Neuroplastic effects of neonatal capsaicin on neurons in adult rat trigeminal nucleus principalis and subnucleus oralis

1996 ◽  
Vol 75 (1) ◽  
pp. 298-310 ◽  
Author(s):  
C. L. Kwan ◽  
J. W. Hu ◽  
B. J. Sessle
Keyword(s):  
Functional Properties ◽  
Mustard Oil ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Adult Rats ◽  
Response Properties ◽  
Adult Rat ◽  
C Fibers ◽  
C Fiber ◽  
Nucleus Principalis

1. The effects of C-fiber depletion induced by neonatal capsaicin treatment on the functional properties of low-threshold mechanoreceptive (LTM) neurons in the rat trigeminal (V) subnucleus oralis and nucleus principalis were examined. Neonatal rats were injected with capsaicin within 48 h of birth. The mechanoreceptive field (RF) and response properties of 184 oralis LTM neurons and 185 principalis LTM neurons were studied in adult capsaicin-treated rats. These properties were compared with those of 200 oralis LTM neurons and 253 principalis LTM neurons from untreated or vehicle-treated (control) adult rats. 2. The effectiveness of neonatal capsaicin in depleting C fibers was tested by determining the plasma extravasation of Evans blue dye that was induced in the hindlimb skin by the cutaneous application of the C-fiber excitant and inflammatory irritant mustard oil. The amount of extravasation in capsaicin-treated rats was significantly less than that of control rats. 3. Neonatal capsaicin treatment was associated with significant increases in neuronal RF size and in the percentage of neurons with convergent inputs from more than one type of peripheral tissue (e.g., nonsinus hair, vibrissae, glabrous skin/mucosa, subcutaneous structures such as joint or muscle, periodontal ligament) in both subnucleus oralis and nucleus principalis. In subnucleus oralis, neonatal capsaicin treatment produced a significant increase in the percentage of neurons with a RF involving both V1 and V2 divisions, and a significant decrease in the percentage of neurons with a RF restricted to the V1 division. Analogous changes were not observed in nucleus principalis, although for principalis vibrissa-sensitive neurons, neonatal capsaicin treatment was associated with significant increases in the total number of vibrissae per neuronal RF and in the maximal length of the vibrissal row (i.e., the number of vibrissae in the longest row of vibrissae, stimulation of which was effective in activating a given neuron). 4. Neonatal capsaicin treatment did not significantly affect other oralis or principalis neuronal properties, including the percentage of neurons exhibiting spontaneous activity or abnormal response properties (such as habituating tap sensitivity, discontinuous RF, or mixed adaptation properties within the RF). 5. The changes in the functional properties of oralis and principalis LTM neurons induced by neonatal capsaicin treatment are consistent with those previously reported at other levels of the rodent CNS. They provide additional support to the view that C fibers may have an important role in shaping the functional properties of central LTM somatosensory neurons.

C-Fiber Depletion Alters Response Properties of Neurons in Trigeminal Nucleus Principalis

1999 ◽  
Vol 81 (2) ◽  
pp. 435-446 ◽  
Author(s):  
C. L. Kwan ◽  
J. A. Demaro ◽  
J. W. Hu ◽  
M. F. Jacquin ◽  
B. J. Sessle
Keyword(s):  
Functional Properties ◽  
Response Magnitude ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Trigeminal Nucleus ◽  
Response Properties ◽  
C Fibers ◽  
C Fiber ◽  
Nucleus Principalis ◽  
Stimulation Of

Kwan, C. L., J. A. Demaro, J. W. Hu, M. F. Jacquin, and B. J. Sessle. C-fiber depletion alters response properties of neurons in trigeminal nucleus principalis. J. Neurophysiol. 81: 435–446, 1999. The effects of C-fiber depletion induced by neonatal capsaicin treatment on the functional properties of vibrissa-sensitive low-threshold mechanoreceptive (LTM) neurons in the rat trigeminal nucleus principalis were examined in adult rats. Neonatal rats were injected either with capsaicin or its vehicle within 48 h of birth. The depletion of unmyelinated afferents was confirmed by the significant decrease in plasma extravasation of Evan's blue dye induced in the hindlimb skin of capsaicin-treated rats by cutaneous application of mustard oil and by the significant decrease of unmyelinated fibers in both the sciatic and infraorbital nerves. The mechanoreceptive field (RF) and response properties of 31 vibrissa-sensitive neurons in capsaicin-treated rats were compared with those of 32 vibrissa-sensitive neurons in control (untreated or vehicle-treated) rats. The use of electronically controlled mechanical stimuli allowed quantitative analysis of response properties of vibrissa-sensitive neurons; these included the number of center- and surround-RF vibrissae within the RF (i.e., those vibrissae which when stimulated elicited ≥1 and <1 action potential per stimulus, respectively), the response magnitude and latency, and the selectivity of responses to stimulation of vibrissae in different directions with emphasis on combining both the response magnitude and direction of vibrissal deflection in a vector analysis. Neonatal capsaicin treatment was associated with significant increases in the total number of vibrissae, in the number of center-RF vibrissae per neuronal RF, and in the percentage of vibrissa-sensitive neurons that also responded to stimulation of other types of orofacial tissues. Compared with control rats, capsaicin-treated rats showed significant increases in the response magnitude to stimulation of surround-RF vibrissae as well as in response latency variability to stimulation of both center- and surround-RF vibrissae. C-fiber depletion also significantly altered the directional selectivity of responses to stimulation of vibrissae. For neurons with multiple center-RF vibrissae, the proportion of center-RF vibrissae with net vector responses oriented toward the same quadrant was significantly less in capsaicin-treated compared with control rats. These changes in the functional properties of principalis vibrissa-sensitive neurons associated with marked depletion of C-fiber afferents are consistent with similarly induced alterations in LTM neurons studied at other levels of the rodent somatosensory system, and indeed may contribute to alterations previously described in the somatosensory cortex of adult rodents. Furthermore, these results provide additional support to the view that C fibers may have an important role in shaping the functional properties of LTM neurons in central somatosensory pathways.

Effects of GABA Receptor Antagonist on Trigeminal Caudalis Nociceptive Neurons in Normal and Neonatally Capsaicin-Treated Rats

1999 ◽  
Vol 82 (5) ◽  
pp. 2154-2162 ◽  
Author(s):  
Chen Yu Chiang ◽  
Chun L. Kwan ◽  
James W. Hu ◽  
Barry J. Sessle
Keyword(s):  
Receptor Antagonist ◽  
Spontaneous Activity ◽  
Dynamic Range ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Receptor Blockade ◽  
Skin Area ◽  
Adult Rats ◽  
Nociceptive Neurons ◽  
C Fiber

We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-d-aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABAA receptor antagonist bicuculline (BIC) or the GABAB receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Vc nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant. As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABAA receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABAA receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABABreceptor blockade by SAC (i.t.) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABAA receptor–mediated inhibition may be involved in maintaining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABAAreceptor–mediated modulation may be disrupted such that a GABAA receptor–mediated excitation is manifested.

Enhanced lung C-fiber responsiveness in sensitized adult guinea pigs exposed to chronic tobacco smoke

2001 ◽  
Vol 91 (4) ◽  
pp. 1645-1654 ◽  
Author(s):  
Dale R. Bergren
Keyword(s):  
Tobacco Smoke ◽  
Guinea Pigs ◽  
Airway Responsiveness ◽  
Compressed Air ◽  
Sensory Receptor ◽  
Plasma Extravasation ◽  
C Fibers ◽  
C Fiber

Tobacco smoke (TS) exposure induces bronchoconstriction and increases airway secretions and plasma extravasation in certain sensitive individuals, particularly those with asthma. C-fiber activation also induces these effects. Although the mechanism by which chronic TS exposure induces airway dysfunction is not well understood, TS exposure may enhance C-fiber responsiveness. To investigate the effect of chronic TS exposure on C-fiber responsiveness to capsaicin and bradykinin, especially in atopic individuals, we exposed ovalbumin (OA)-sensitized guinea pigs to TS (5 mg/l air, 30 min/day for 7 days/wk) or to compressed air. Nonsensitized guinea pigs were also exposed to either compressed air or TS. Beginning after 120 days of exposure, C fibers and rapidly adapting receptors (RARs) were challenged with capsaicin and bradykinin. TS exposure enhanced sensory receptor and airway responsiveness to both intravenous capsaicin and bradykinin challenge. C-fiber, RAR, and airway responsiveness to capsaicin challenge was greatest in OA-sensitized guinea pigs exposed to TS. OA alone induced capsaicin hyperresponsiveness at 5 μg. Airway responsiveness to bradykinin was also greatest in OA-sensitized guinea pigs exposed to TS. OA alone enhanced C-fiber responsiveness to bradykinin at 5 and 10 μg. C-fiber activation by either agonist appeared direct, whereas RAR activation appeared indirect. Therefore, a mechanism of airway hyperirritability induced by the combination of OA sensitization and chronic TS exposure may include hyperirritability of lung C fibers.

scholarly journals Pulmonary C-fiber activation attenuates respiratory-related tongue movements

2012 ◽  
Vol 113 (9) ◽  
pp. 1369-1376 ◽  
Author(s):  
Kun-Ze Lee ◽  
David D. Fuller ◽  
Ji-Chuu Hwang
Keyword(s):  
Upper Airway ◽  
Respiratory Drive ◽  
Adult Rats ◽  
Nerve Branch ◽  
Airway Patency ◽  
C Fibers ◽  
Tongue Muscles ◽  
C Fiber ◽  
Before And After ◽  
Tongue Movements

The functional impact of pulmonary C-fiber activation on upper airway biomechanics has not been evaluated. Here, we tested the hypothesis that pulmonary C-fiber activation alters the respiratory-related control of tongue movements. The force produced by tongue movements was quantified in spontaneously breathing, anesthetized adult rats before and after stimulation of pulmonary C fibers via intrajugular delivery of capsaicin (0.625 and 1.25 μg/kg). Brief occlusion of the trachea was used to increase the respiratory drive to the tongue muscles, and hypoglossal (XII) nerve branches were selectively sectioned to denervate the protrusive and retrusive tongue musculature. Tracheal occlusion triggered inspiratory-related tongue retrusion in rats with XII nerves intact or following section of the medial XII nerve branch, which innervates the genioglossus muscle. Inspiratory-related tongue protrusion was only observed after section of the lateral XII branch, which innervates the primary tongue retrusor muscles. The tension produced by inspiratory-related tongue movement was significantly attenuated by capsaicin, but tongue movements remained retrusive, unless the medial XII branch was sectioned. Capsaicin also significantly delayed the onset of tongue movements such that tongue forces could not be detected until after onset of the inspiratory diaphragm activity. We conclude that altered neural drive to the tongue muscles following pulmonary C-fiber activation has a functionally significant effect on tongue movements. The diminished tongue force and delay in the onset of tongue movements following pulmonary C-fiber activation are potentially unfavorable for upper airway patency.

Protective role for neuropeptides in acute pulmonary response to acrolein in guinea pigs

1993 ◽  
Vol 75 (6) ◽  
pp. 2456-2465 ◽  
Author(s):  
C. R. Turner ◽  
R. B. Stow ◽  
S. D. Talerico ◽  
E. P. Christian ◽  
J. C. Williams
Keyword(s):  
Guinea Pigs ◽  
Pulmonary Inflammation ◽  
Retrograde Transport ◽  
Protective Role ◽  
Neuronal Uptake ◽  
Blue Dye ◽  
Airway Epithelial ◽  
Neuronal Viability ◽  
C Fibers ◽  
C Fiber

To determine the potential role of neuropeptides in acrolein-induced airway responses, capsaicin-treated guinea pigs were exposed to acrolein aerosol in a regimen causing increased airway sensitivity to substance P. Acrolein exposure resulted in 100% mortality after capsaicin pretreatment compared with only 14% mortality in guinea pigs not pretreated with capsaicin. Acrolein exposure by itself caused marked pulmonary inflammation and large airway epithelial necrosis and denudation. Pretreatment with capsaicin exacerbated these responses throughout the lung. Intravenous acrolein caused an acute dose-related bronchoconstriction in naive guinea pigs that was diminished by capsaicin treatment and potentiated by thiorphan pretreatment, which suggests that arolein exposure causes an acute release of capsaicin-sensitive C-fiber neuropeptides. To determine whether acrolein-induced C-fiber release altered neuronal viability, either rhodamine or Fast Blue dye was instilled intratracheally into vehicle- or acrolein-exposed guinea pigs. Acrolein exposure did not reduce the neuronal uptake or retrograde transport of these dyes, as indicated by the number of fluorescent cell bodies in the nodose ganglia. To determine the functional state of airway neurons, the dose response to intravenous capsaicin was measured in vehicle-exposed and acrolein-exposed guinea pigs; no differences were observed. Thus, acrolein appears to activate airway C-fibers, which release neuropeptides that are protective against this insult, with no suggestion of an accompanying reduction in C-fiber function.

Neurogenically Mediated Plasma Extravasation in Dura Mater: Effect of Ergot Alkaloids: A Possible Mechanism of Action in Vascular Headache

Cephalalgia ◽  
1988 ◽  
Vol 8 (2) ◽  
pp. 83-91 ◽  
Author(s):  
Stephen Markowitz ◽  
Kiyoshi Saito ◽  
Michael A Moskowitz
Keyword(s):  
Dura Mater ◽  
Sensory Nerve ◽  
Ergot Alkaloids ◽  
Nerve Fibers ◽  
Neurokinin A ◽  
Acute Administration ◽  
Plasma Extravasation ◽  
C Fibers ◽  
C Fiber ◽  
Stimulation Of

C-fiber- dependent neurogenic plasma extravasation developed in the dura mater but not the brain after electric stimulation of the rat trigeminal ganglion or after chemical stimulation of perivascular axons with intravenous capsaicin, a drug that depolarizes sensory nerve fibers. C-fiber- independent extravasation also developed in this tissue after intravenous injections of substance P or neurokinin A (two constituents of unmyelinated C fibers) and after serotonin, bradykinin, or allergic challenge in presensitized animals. Intravenous dihydroergotamine or ergotamine tartrate, in doses similar to those used to treat migraine and cluster headache, prevented the stimulation-induced leakage of plasma proteins within the dura mater. Not unexpectedly, the acute administration of methysergide, a drug effective in the prophylactic treatment of headache, was inactive in this acute model. Neither acute nor chronic administration of propranolol affected stimulation-induced leakage of plasma protein. These results demonstrate that neurogenic inflammation develops within the dura mater in the rat and that ergot alkaloids prevent the process by a C-fiber-dependent mechanism.

Sensitization of nociceptive C-fibers in zinc-deficient rats

1995 ◽  
Vol 268 (6) ◽  
pp. R1423-R1428 ◽  
Author(s):  
H. Izumi ◽  
H. Mori ◽  
T. Uchiyama ◽  
S. Kuwazuru ◽  
Y. Ozima ◽  
...  
Keyword(s):  
Substance P ◽  
Zinc Concentration ◽  
Leukotriene B4 ◽  
Plasma Extravasation ◽  
Deficient Diet ◽  
C Fibers ◽  
Pge2 Concentration ◽  
Antidromic Vasodilatation ◽  
C Fiber ◽  
Zinc Deficient Diet

A marked decrease in zinc concentration was observed in plasma (P < 0.001), hindpaw skin (P < 0.01), and dorsal skin (P < 0.01) in zinc-deficient rats (rats fed a zinc-deficient diet for 3 wk), compared with the control rats fed the same zinc-deficient diet supplemented with ZnCO3 (50 mg/kg diet). The threshold intensity needed to elicit vasodilatation in the hindpaw skin of the zinc-deficient rats on electrical stimulation of the saphenous nerve in a peripheral direction was markedly lower (P < 0.01) than that in the control rats. No difference was observed between control (n = 5) and zinc-deficient rats (n = 5) in the magnitude of the plasma extravasation evoked by either histamine or substance P. There was no difference between control and zinc-deficient rats in terms of the dose-response curve for release of histamine by substance P. Prostaglandin E2 (PGE2) concentration in the hindpaw skin of the zinc-deficient rats was nearly fourfold higher (P < 0.01) than that of the control rats, whereas no difference in the leukotriene B4 level in the hindpaw skin was observed between control and zinc-deficient rats. From the present study, it seems likely that an increased level of PGE2 in the vicinity of the nociceptive C-fiber terminals in the hindpaw skin of zinc-deficient rats may sensitize the terminals of the nociceptive C-fibers of the saphenous afferent nerve in the hindpaw and thus facilitate the production of antidromic vasodilatation.

Neurophysiological basis for neurogenic-mediated articular cartilage anabolism alteration

2001 ◽  
Vol 280 (1) ◽  
pp. R115-R122 ◽  
Author(s):  
Elvire Gouze-Decaris ◽  
Lionel Philippe ◽  
Alain Minn ◽  
Philippe Haouzi ◽  
Pierre Gillet ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Cartilage Damage ◽  
Intrathecal Injection ◽  
Chronic Administration ◽  
C Fibers ◽  
Glutamatergic Synaptic Transmission ◽  
C Fiber ◽  
Fiber Stimulation ◽  
Neurophysiological Basis

This study was designed to investigate the pathways involved in neurogenic-mediated articular cartilage damage triggered by a nonsystemic distant subcutaneous or intra-articular inflammation. The cartilage damage was assessed 24 h after subcutaneous or intra-articular complete Freund's adjuvant (CFA) injection measuring patellar proteoglycan (PG) synthesis (ex vivo [Na2 35SO4] incorporation) in 96 Wistar rats. Unilateral subcutaneous or intra-articular injection of CFA induced significant decrease (25–29%) in PG synthesis in both patellae. Chronic administration of capsaicin (50 mg · kg−1 · day−1 during 4 days), which blunted the normal response of C fiber stimulation, prevented the bilateral significant decrease in cartilage synthesis. Similarly, intrathecal injection of MK-801 (10 nmol/day during 5 days), which blocked the glutamatergic synaptic transmission at the dorsal horn of signal originating in primary afferent C fibers, eliminated the CFA-induced PG synthesis decrease in both patellae. Chemical sympathectomy, induced by guanethidine (12.5 mg · kg−1 · day−1 during 6 wk), also prevented PG synthesis alteration. Finally, compression of the spinal cord at the T3-T5 level had a similar protective effect on the reduction of [Na2 35SO4] incorporation. It is concluded that the signal that triggers articular cartilage synthesis damage induced by a distant local inflammation 1) is transmitted through the afferent C fibers, 2) makes glutamatergic synaptic connections with the preganglionic neurons of the sympathetic system, and 3) involves spinal and supraspinal pathways.

Differential blockade of cat dorsal root C fibers by various chloride solutions

1972 ◽  
Vol 36 (5) ◽  
pp. 569-583 ◽  
Author(s):  
J. Stovall King ◽  
Don L. Jewett ◽  
Howard R. Sundberg
Keyword(s):  
Hypertonic Saline ◽  
Choline Chloride ◽  
Isotonic Saline ◽  
Chloride Ion ◽  
Content Type ◽  
Persistent Effect ◽  
C Fibers ◽  
C Fiber ◽  
Intrathecal Infusion

✓ A possible mechanism by which intrathecal infusion of partially frozen saline might relieve patients of chronic pain has been studied by applying hypertonic saline to the dorsal rootlets of cats in vitro. The supernatant of partially thawed normal saline was found to be hypertonic. Persistent block of C fibers, detected by a collision method, occurred after the rootlets had been exposed to saline from 500 to 2500 mOsm/L for 15 min followed by 15 min of isotonic saline. Few of the A fibers were blocked by this procedure, but both A and C fibers were blocked when solutions of 3500 mOsm/L were used. Differential blockage of C fibers could also be produced with hypotonic saline and with distilled water. Localized cooling, to 2°C for 25 min, had no persistent effect on C fiber conduction, and when cooling was combined with hypertonic saline there was no potentiation of the differential blockade caused by the saline. Hypertonic solutions of sucrose or sodium nitrate produced no persistent differential block; most A and C fibers recovered. However, choline chloride was as effective as sodium chloride in giving a differential blockade. It seems that chloride ion plays a major role in establishing the persistent C fiber blockade observed when dorsal rootlets are exposed to hypertonic saline.

Plasma extravasation induced by neurokinins in conscious rats: receptor characterization with agonists and antagonists

1993 ◽  
Vol 71 (3-4) ◽  
pp. 217-221 ◽  
Author(s):  
Mauro Nicolau ◽  
Martin G. Sirois ◽  
Michel Bui ◽  
Gérard E. Plante ◽  
Pierre Sirois ◽  
...  
Keyword(s):  
Substance P ◽  
Urinary Bladder ◽  
Vascular Permeability ◽  
Blue Dye ◽  
Receptor Subtype ◽  
Plasma Extravasation ◽  
Functional Sites ◽  
Conscious Rats ◽  
Selective Antagonists ◽  
Selective Agonists

The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [βAla8]NKA(4–10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [βAla8]NKA(4–10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists. SR 48968 (500 nmol/kg) was inactive against substance P as well as against the NK-2 or NK-3 selective agonists. RP 67580 (250 nmol/kg), CP-96,345 (250 nmol/kg), and SR 48968 (500 nmol/kg) per se did not induce any plasma extravasation, except in the urinary bladder, where CP-96,345 and SR 48968 increased EB concentrations in the tissue. These results suggest that the effects of neurokinins on vascular permeability vary from one tissue to another. The blockade of substance P by the NK-1 receptor selective antagonists, RP 67580 and CP-96,345, suggests that NK-1 receptors play an important role in the plasma extravasation induced by substance P. However, the effects of NK-2 and NK-3 receptor selective agonists appear to be independent of activation of NK-1 receptors since they are not blocked by RP 67580 or CP-96,345. Furthermore, because the effect of [βAla8]NKA(4–10), the NK-2 selective agonist, was not abolished by SR 48968, it is suggested that it might be mediated by the NK-2 receptor subtype NK-2B, which is less sensitive to SR 48968 than is NK-2A. The contribution of NK-3 receptors to plasma extravasation could not be adequately demonstrated in the present study because NK-3 antagonists sufficiently active in vivo are not available.Key words: neurokinins, RP 67580, CP-96,345, SR 48968, vascular permeability.

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