Characterization of the effects of neurokinins on canine antral muscle

1988 ◽  
Vol 255 (6) ◽  
pp. G779-G786
Author(s):  
C. B. Koelbel ◽  
E. A. Mayer ◽  
G. van Deventer ◽  
W. J. Snape ◽  
A. Patel
Keyword(s):  
Substance P ◽  
Mechanical Response ◽  
Longitudinal Muscle ◽  
Rank Order ◽  
Circular Muscle ◽  
Neurokinin A ◽  
Inotropic Response ◽  
Chronotropic Response ◽  
Natural Ligand ◽  
Dose Dependent

The excitation of longitudinal antral muscle by substance P (SP) involves both a myogenic and a cholinergic effect. To examine if these responses are mediated by different neurokinin receptors, we studied the mechanical response and the release of [3H]acetylcholine from antral muscle strips in response to SP, substance P methylester (SPME), neurokinin A (NKA), neurokinin B (NKB), and several non-mammalian tachykinins. All peptides studied showed a dose-dependent inotropic and chronotropic effect on spontaneous phasic contractions. This ionotropic effect in longitudinal muscle was partially atropine sensitive for SPME, SP, and NKB but not for NKA, whereas neither atropine nor tetrodotoxin had an effect in circular muscle. In longitudinal muscle, all three neurokinins were equipotent. In longitudinal muscle treated with atropine and in circular muscle, the rank order of potency for the inotropic response was NKA greater than NKB greater than SP greater than SPME. For the chronotropic response the rank order was SPME, SP greater than NKA greater than NKB. NKA, NKB, and SP caused a dose-dependent, tetrodotoxin-sensitive increase in [3H]acetylcholine release from strips preincubated with [3H]choline. NKA was significantly more potent to release [3H]acetylcholine than either NKB or SP. The stimulated release was inhibited by [D-Ala2,D-Met5]methionine enkephalinamide and the SP antagonist, spantide. These results are consistent with the hypothesis that NKA is the natural ligand mediating the myogenic inotropic response in both muscle layers and the cholinergic response in longitudinal muscle.

Involvement of substance P in noncholinergic excitation of rabbit colonic muscle

1989 ◽  
Vol 256 (1) ◽  
pp. G246-G253 ◽  
Author(s):  
C. B. Koelbel ◽  
E. A. Mayer ◽  
J. R. Reeve ◽  
W. J. Snape ◽  
A. Patel ◽  
...  
Keyword(s):  
Substance P ◽  
Mechanical Response ◽  
Longitudinal Muscle ◽  
Rank Order ◽  
Distal Colon ◽  
Neurokinin A ◽  
Excitatory Neurotransmitters ◽  
Biological Potency ◽  
Potent Agonist ◽  
Dose Dependent

Neurokinins have been implicated as noncholinergic excitatory neurotransmitters in the mammalian gastrointestinal tract. To characterize the myogenic and neurogenic response of colonic muscle to neurokinins we studied the mechanical response of muscle strips from proximal and distal colon and the release of [3H]acetylcholine in response to substance P (SP), neurokinin A (NKA) and neurokinin B (NKB). All neurokinins caused a dose-dependent inotropic response. SP was 80 times more potent in distal compared with proximal longitudinal muscle. The rank order of potencies in proximal longitudinal muscle was NKA greater than SP = NKB and in distal muscle NKA = SP = NKB. Desensitization to SP or pretreatment with a SP antagonist inhibited the mechanical response to SP and the atropine-resistant inotropic off response to electrical stimulation. Only longitudinal muscle from distal colon had an atropine- and hexamethonium-sensitive inotropic component to SP. In contrast, all three peptides were equipotent in releasing [3H]acetylcholine from longitudinal muscle strips preincubated with [3H]choline. These results suggest the following: 1) SP is a potent agonist of rabbit colon with a proximal distal gradient in biological potency; 2) the myogenic response of the distal colon appears to be mediated through a NK-1 receptor; and 3) SP is a major mediator of the noncholinergic component of the off response in distal longitudinal muscle.

Somatostatin modulates cholinergic neurotransmission in canine antral muscle

1988 ◽  
Vol 254 (2) ◽  
pp. G201-G209 ◽  
Author(s):  
C. B. Koelbel ◽  
G. van Deventer ◽  
S. Khawaja ◽  
M. Mogard ◽  
J. H. Walsh ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Substance P ◽  
Prostaglandin E2 ◽  
Positive Inotropic Effect ◽  
Mechanical Response ◽  
Inhibitory Effect ◽  
Inotropic Effect ◽  
Inotropic Response ◽  
Cholinergic Neurotransmission

Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of [3H]acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, somatostatin had a positive inotropic effect on spontaneous phasic contractions. In tissues stimulated with substance P and gastrin 17, but not with electrical stimulation, somatostatin inhibited the phasic inotropic response dose dependently. This inhibitory effect was abolished by indomethacin. Somatostatin stimulated the release of prostaglandin E2 radioimmunoreactivity, and prostaglandin E2 inhibited the release of [3H]acetylcholine induced by substance P and electrical stimulation. Somatostatin increased the release of [3H]acetylcholine from unstimulated tissues by a tetrodotoxin-sensitive mechanism but inhibited the release induced by substance P and electrical stimulation. These results suggest that somatostatin has a dual modulatory effect on cholinergic neurotransmission in canine longitudinal antral muscle. This effect is excitatory in unstimulated tissues and inhibitory in stimulated tissues. The inhibitory effect is partially mediated by prostaglandins.

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs

1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  
Keyword(s):  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Neurokinin A ◽  
Dependent Manner ◽  
C Fiber ◽  
Dose Dependent

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

Downregulation of neutral endopeptidase (EC 3.4.24.11) in the inflamed rat intestine

1993 ◽  
Vol 264 (4) ◽  
pp. G735-G743 ◽  
Author(s):  
L. Hwang ◽  
R. Leichter ◽  
A. Okamoto ◽  
D. Payan ◽  
S. M. Collins ◽  
...  
Keyword(s):  
Substance P ◽  
Myenteric Plexus ◽  
Longitudinal Muscle ◽  
Intestinal Inflammation ◽  
Specific Activity ◽  
Trichinella Spiralis ◽  
Extracellular Fluid ◽  
Circular Muscle ◽  
Neutral Endopeptidase ◽  
Jejunal Mucosa

Intestinal inflammation induced by the nematode Trichinella spiralis is accompanied by increased intestinal concentrations of substance P, a mediator of inflammation and a stimulant of smooth muscle contraction, and by intestinal hypermotility. The expression of neutral endopeptidase (NEP), a cell surface enzyme that degrades substance P in the extracellular fluid, was examined in the inflamed intestine. NEP enzymatic activity, measured by a fluorometric assay, was reduced by 84-fold in jejunal mucosa-circular muscle and by 12-fold in jejunal longitudinal muscle-myenteric plexus within 6 days after infection with T. spiralis. The downregulation was unaffected by treatment with betamethasone and was still observed in athymic animals. NEP protein levels, examined by Western blotting, confirmed the loss of NEP from inflamed tissue. The specific activity for degradation of substance P was reduced by sixfold in jejunal mucosa-circular muscle and by twofold in jejunal longitudinal muscle-myenteric plexus of rats infected with T. spiralis compared with uninfected controls. Thus the downregulation of NEP resulted in reduced substance P degradation, which may contribute to functional abnormalities of the inflamed intestine.

Proteolytic Inactivation of Substance P and Neurokinin A in the Longitudinal Muscle Layer of Guinea Pig Small Intestine

2006 ◽  
Vol 47 (3) ◽  
pp. 856-864 ◽  
Author(s):  
R. Nau ◽  
G. Schäfer ◽  
C. F. Deacon ◽  
T. Cole ◽  
D. V. Agoston ◽  
...  
Keyword(s):  
Small Intestine ◽  
Substance P ◽  
Guinea Pig ◽  
Longitudinal Muscle ◽  
Muscle Layer ◽  
Neurokinin A ◽  
Longitudinal Muscle Layer

Substance P and CGRP mediate motor response of rabbit colon to capsaicin

1990 ◽  
Vol 259 (5) ◽  
pp. G889-G897 ◽  
Author(s):  
E. A. Mayer ◽  
C. B. Koelbel ◽  
W. J. Snape ◽  
V. Eysselein ◽  
H. Ennes ◽  
...  
Keyword(s):  
Substance P ◽  
Longitudinal Muscle ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Inhibitory Effect ◽  
Nerve Fibers ◽  
Repeated Exposure ◽  
Nerve Terminals ◽  
Rabbit Colon

Primary afferent nerve terminals located in the mammalian gut wall may play a role in region-specific modulation of gastrointestinal motility. In the present study, we sought to characterize the effect of neuropeptides released from these afferents by capsaicin (CAP) on contractile activity of smooth muscle from the distal rabbit colon. CAP caused a release of acetylcholine and immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) from the muscle coat. CAP caused a dose-dependent transient stimulation of longitudinal muscle contractions, followed by prolonged inhibition of spontaneous but not stimulated contractile activity. The initial stimulation was abolished by the SP antagonist spantide and by atropine. The inhibitory effect was reduced by repeated exposure of muscle to CGRP. The effect of CGRP on spontaneous contractions differed between longitudinal and circular muscle. In longitudinal muscle, a stimulation was preceded by a transient inhibition, whereas in circular muscle, only inhibition was seen. Both effects were resistant to tetrodotoxin. Repeated exposure of circular but not longitudinal muscle to CGRP resulted in a disappearance of the peptide's inhibitory effect. Exogenously applied CGRP was only a weak antagonist of contractions stimulated by SP and bethanechol. These findings suggest that in the rabbit colon at least the following two neuropeptides are released from CAP-sensitive nerve fibers: a neurokinin peptide from nerve terminals located within the myenteric plexus and CGRP from terminals probably located within the circular muscle layer.

Differential effects of [Gln4]neurotensin on circular and longitudinal muscle of dog ileum in vitro

1987 ◽  
Vol 253 (4) ◽  
pp. G566-G572
Author(s):  
M. Karaus ◽  
K. R. Prasad ◽  
S. K. Sarna ◽  
I. M. Lang
Keyword(s):  
Longitudinal Muscle ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Cholinergic Nerves ◽  
Differential Effects ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Muscle Contractile

We studied the effects of neurotensin analogue [Gln4]-neurotensin on isolated dog ileal longitudinal and circular muscle strips. [Gln4]neurotensin stimulated the spontaneous contractile activity of the circular muscle but inhibited that of the longitudinal muscle in a dose-dependent fashion. Hexamethonium had no effect on the spontaneous longitudinal or circular muscle contractile activity. Atropine and tetrodotoxin (TTX) both inhibited the longitudinal muscle. Atropine had no effect on the circular muscle, but TTX stimulated it. The effects of [Gln4]neurotensin on the circular muscle were reduced but not completely abolished by atropine. The inhibition of the longitudinal muscle by [Gln4]neurotensin was not reduced by any of the above antagonists but was enhanced by atropine. Electrical field stimulation (10 Hz, 100 mA) stimulated the longitudinal muscle and inhibited or stimulated the circular muscle depending on the pulse width of the stimulus. These effects were unaffected by [Gln4]neurotensin. We conclude that [Gln4]neurotensin has differential effects on isolated muscle strips of the two muscle layers in the dog ileum. It stimulates the circular muscle partially through cholinergic nerves at preganglionic sites and partially through a direct myogenic effect. [Gln4]neurotensin inhibits the spontaneous activity of the longitudinal muscle presumably by reducing the excitability of cholinergic nerves at postganglionic sites.

Tachykinin-mediated increase in motility acts independently of vasoactive intestinal polypeptide release in the canine ileum

1994 ◽  
Vol 72 (2) ◽  
pp. 109-112 ◽  
Author(s):  
E. G. Watson ◽  
J. E. T. Fox-Threlkeld ◽  
E. E. Daniel
Keyword(s):  
Gastrointestinal Tract ◽  
Substance P ◽  
Motor Activity ◽  
Vasoactive Intestinal Polypeptide ◽  
Neurokinin A ◽  
Significant Change ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Intestinal Polypeptide

Tachykinins induce motor activity in the canine ileum, and their mechanism of excitation may include inhibition of the release of a nonadrenergic, noncholinergic inhibitor, for which vasoactive intestinal polypeptide (VIP) is a candidate. Both substance P and neurokinin A produced a dose-dependent increase in ileal contractility with no significant change in VIP output. The highly selective NK1 agonist [Sar9, Met(O2)11]substance P and the highly selective NK2 agonist [Nle10]neurokinin A (4–10) also increased motor activity in the absence of any change in VIP released. These data suggest that the tachykinins produce motor activity in the canine ileum via a mechanism that does not involve changes in VIP output but may involve excitation through both NK1 and NK2 receptors.Key words: vasoactive intestinal polypeptide, tachykinins, gastrointestinal tract, motility.

Mechanics and neuropeptide responses of feline pylorus and gastric muscle in vitro

1989 ◽  
Vol 256 (5) ◽  
pp. G862-G867 ◽  
Author(s):  
A. Merlo ◽  
S. Cohen
Keyword(s):  
Substance P ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Optimal Length ◽  
Pyloric Ring ◽  
Tension Properties ◽  
Gastric Muscle ◽  
Inferior Portion ◽  
Superior Portion

Mechanical properties and neuropeptide responses were compared for feline pyloric and gastric muscle under isometric conditions in vitro. Total tension in antral circular muscle (0.699 +/- 0.003 kg/cm2) was less than in corpus circular (1.597 +/- 0.007 kg/cm2) or longitudinal muscle from the lesser and greater curvatures (1.256 +/- 0.009 and 1.253 +/- 0.007 kg/cm2, n greater than or equal to 55, P less than 0.05). The components of tension at optimal length were similar for all gastric muscles (P greater than 0.1). The pylorus maintained less total tension (0.335 +/- 0.003 kg/cm2) and a greater component of resting tension (75.6%) than gastric muscle (P less than 0.01). Substance P, cholecystokinin-8 (CCK-8), and neurotensin varied in potency and efficacy in circular muscle of the antrum, corpus, and inferior portion of the pyloric ring. Longitudinal muscle and the superior portion of pylorus responded poorly if at all to neuropeptides. Substance P- but not CCK-8- or neurotensin-induced contractions of gastric muscle were reduced by tetrodotoxin (TTX) and atropine (P less than 0.05). Substance P-induced pyloric contractions were TTX sensitive (P less than 0.05) but were unaffected by atropine. We concluded that 1) length-tension properties of gastric muscle are similar and distinct from the pylorus and that 2) neuropeptide efficacy varies regionally within the feline stomach and within the pylorus.

Neuropeptide responses and mechanics of the proximal and distal feline colon in vitro

1988 ◽  
Vol 255 (6) ◽  
pp. G787-G793
Author(s):  
A. Merlo ◽  
S. Cohen
Keyword(s):  
Mechanical Properties ◽  
Substance P ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Isometric Contractions ◽  
Active Tension ◽  
Intrinsic Properties ◽  
Cholecystokinin Octapeptide ◽  
Anatomic Region

Mechanical properties and responses to neuropeptides were compared for proximal and distal feline colonic muscle. Proximal longitudinal (PL), proximal circular (PC), distal longitudinal (DL), and distal circular (DC) muscles were studied in vitro under isometric conditions. Total tension in DL [1.636 +/- 0.009 (SE) kg/cm2] was greater than in DC (0.699 +/- 0.004 kg/cm2) or PC (0.710 +/- 0.005 kg/cm2, P less than 0.05). Longitudinal muscle developed proportionately more active tension than circular muscle at each region (80.9% in DL vs. 54.1% in DC and 77.1% in PL vs. 52.3% in PC, P less than 0.01). Neuropeptides varied in potency and efficacy. Cholecystokinin octapeptide (CCK-8) was the most potent and efficacious in PL and substance P was the most efficacious in PC muscle (P less than 0.05). Substance P was more efficacious whereas CCK-8 and neurotensin were less efficacious in PC than PL muscle (P less than 0.01). DL muscle did not respond to CCK-8. DC muscle did not respond to CCK-8 or neurotensin. Isometric contractions to each neuropeptide were insensitive to tetrodotoxin. We conclude that 1) mechanical properties of circular and longitudinal colonic muscle differ and 2) responses to neuropeptides depend on anatomic region and intrinsic properties.

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