Relaxation of isolated human corpus spongiosum induced by vasoactive intestinal polypeptide, substance P, carbachol and electrical field stimulation

The effects of the nitric oxide (NO) synthesis inhibitors, NG-nitro-L-arginine (L-NNA) and NG-nitro-L-arginine methyl ester (L-NAME), on the electrical field stimulation (EFS)-induced inhibitory responses were investigated. EFS caused, in strips contracted by means of substance P (SP), prostaglandin F2 alpha (PGF2 alpha), or carbachol (CCh), a fast relaxant response that, depending on stimulation frequency and strip tension, could be followed by a slower, sustained relaxation. The NO synthesis inhibitors blocked the EFS-induced fast relaxations and often reversed them into contractions; these effects were greatly counteracted in SP- or PGF2 alpha-treated strips by scopolamine or atropine. In CCh-precontracted strips, either L-NNA or L-NAME became progressively unable to block the EFS-induced fast relaxations as the CCh concentration was increased. The NO synthesis inhibitors greatly reduced the sustained relaxant responses elicited either by EFS or exogenous vasoactive intestinal polypeptide (VIP). The results indicate that the NO synthesis inhibitors abolish the neurally induced fast relaxation by interfering with the cholinergic excitatory pathway. The involvement of both VIP and NO in sustained relaxations is also suggested.

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Substance P enhances electrical field stimulation-induced mast cell degranulation in rat trachea

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.6.l985 ◽

1996 ◽

Vol 270 (6) ◽

pp. L985-L991 ◽

Cited By ~ 3

Author(s):

X. Y. Hua ◽

S. M. Back ◽

E. K. Tam

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Substance P ◽

Electrical Field Stimulation ◽

Mast Cell Degranulation ◽

Facilitatory Effect ◽

Neurokinin A ◽

Field Stimulation ◽

Cell Secretion ◽

Electrical Field

We previously demonstrated in an ex vivo rat tracheal model that chymotryptic activity is an index of mast cell degranulation and that substance P (SP) and electrical field stimulation (EFS) synergistically degranulate mucosal and connective tissue mast cells. In the current study, we found that the facilitatory effect of SP was apparent at concentrations as low as 10(-9) M. This effect was mimicked by 10(-7) M neurokinin A or by 10(-6) M capsaicin and was blocked by the NK1 receptor antagonist CP-96,345. SP + EFS-induced mast cell secretion was significantly attenuated by 10(-6) M tetrodotoxin. The response was also attenuated in tracheas from rats in which sensory nerves had been depleted by systemic pretreatment with capsaicin or in which sympathetic nerves had been depleted by systemic pretreatment with 6-hydroxy-dopamine. Atropine (10(-6) M) or indomethacin (10(-5) M) also attenuated SP + EFS-induced mast cell secretion. Our findings suggest the importance of a sensitizing rather than a direct stimulating effect of SP on mast cell degranulation. SP may increase the sensitivity of mast cells to EFS-discharged mediators or facilitate the release of mast cell-stimulating mediators from autonomic nerves.

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Effect of hyperoxia on substance P expression and airway reactivity in the developing lung

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.273.1.l40 ◽

1997 ◽

Vol 273 (1) ◽

pp. L40-L45 ◽

Cited By ~ 13

Author(s):

F. H. Agani ◽

N. T. Kuo ◽

C. H. Chang ◽

I. A. Dreshaj ◽

C. F. Farver ◽

...

Keyword(s):

Substance P ◽

Electrical Field Stimulation ◽

Postnatal Life ◽

Field Stimulation ◽

Nk1 Receptor ◽

Cholinergic Stimulation ◽

Airway Reactivity ◽

Electrical Field ◽

Contractile Responses

This study was undertaken to characterize changes in the tachykinin system induced by hyperoxic exposure and the potential effects on airway contractile responses. We exposed 7-day-old rat pups to either room air or hyperoxia (> 95% O2) for 7 days to assess pulmonary beta-preprotachykinin (beta-PPT) gene expression, substance P (SP) levels, and airway contractile responses to cholinergic stimulation before and after neurokinin-1 (NK1) receptor blockade. Lung beta-PPT mRNA expression, lung and tracheal SP levels, and contractile responses to exogenous acetylcholine and electrical field stimulation were measured in vitro in normoxia- and hyperoxia-exposed tracheal cylinders. Hyperoxia caused a 1.1- to 2.6-fold increase in steady-state lung beta-PPT mRNA and a 50 and 32% increase in SP levels of lung and trachea, respectively. In response to cholinergic stimulation, maximal contractile force (Emax) of hyperoxia exposed tracheal muscle was significantly higher than for normoxic controls. Addition of the SP (NK1) receptor blocker CP-99994 (10 microM) decreased sensitivity to electrical field stimulation in both hyperoxic and normoxic trachea without a significant decline in Emax. These data provide evidence for both increased SP production and enhanced maximal contractile responses of hyperoxia-exposed neonatal trachea to cholinergic stimulation. The tachykinin peptide SP does not, however, appear to play a major role in the enhanced airway reactivity associated with hyperoxic lung injury during early postnatal life.

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Biphasic relaxation of the opossum lower esophageal sphincter: roles of NO ⋅, VIP, and CGRP

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.3.g548 ◽

1999 ◽

Vol 277 (3) ◽

pp. G548-G554 ◽

Cited By ~ 6

Author(s):

Aliye Uc ◽

S. T. Oh ◽

Joseph A. Murray ◽

Eugene Clark ◽

Jeffrey L. Conklin

Keyword(s):

Nitric Oxide ◽

Lower Esophageal Sphincter ◽

Vasoactive Intestinal Polypeptide ◽

Electrical Field Stimulation ◽

Field Stimulation ◽

Electrical Field ◽

Calcitonin Gene ◽

Esophageal Sphincter ◽

Cgrp Antagonist ◽

Transverse Muscle

Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO ⋅) are thought to mediate lower esophageal sphincter (LES) relaxation. Transverse muscle strips from the opossum LES were used to test this hypothesis. Electrical field stimulation (EFS) produced a biphasic LES relaxation: a rapid component during the stimulus was more prominent at lower stimulus frequencies, and a sustained component was more prominent at higher frequencies. N ω-nitro-l-arginine and hemoglobin inhibited the rapid component but affected the sustained component less. Exogenous VIP decreased LES tone. A number of purported VIP antagonists blocked neither VIP-induced nor EFS-induced relaxation of the LES. The calcitonin gene-related peptide (CGRP) antagonist CGRP-(8—37) did not alter EFS-induced LES relaxation. EFS-induced relaxation of opossum LES muscle is biphasic, and the initial, rapid component of the relaxation is mediated primarily by NO ⋅. The mediator of the sustained component was not identified.

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Influence of maturation on constrictive response to stimulation of C-fiber afferents in isolated guinea pig airways

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00156.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. L168-L175 ◽

Cited By ~ 2

Author(s):

Z.-X. Wu ◽

Q. H. Yang ◽

T. Ruan ◽

L.-Y. Lee

Keyword(s):

Substance P ◽

Guinea Pigs ◽

Main Bronchus ◽

Electrical Field Stimulation ◽

Neurokinin A ◽

Field Stimulation ◽

Response Curves ◽

Electrical Field ◽

C Fiber ◽

Stimulation Of

We investigated whether the airway constrictive response to stimulation of bronchopulmonary C-fiber afferents is altered during the maturation process. Isometric tension was measured in airway rings isolated from three tracheobronchial locations (intrathoracic trachea and main and hilar bronchi) and compared in mature [M, 407 ± 10 (SE) g body wt, n = 36] and immature (IM, 161 ± 5 g body wt, n = 35) guinea pigs. Our results showed no difference in the ACh (10−5 M)- or KCl (40 mM)-induced contraction between M and IM groups, regardless of the airway location. In sharp contrast, the concentration-response curves of 10−8–10−6 M capsaicin were distinctly lower in IM hilar bronchi; for example, response to the same concentration of capsaicin (10−6 M) was 89.2 ± 15.3% of the response to 10−5 M ACh in IM and 284.7 ± 43.2% in M animals. Similar, but smaller, differences in the bronchoconstrictive response to capsaicin between IM and M groups were also observed in the trachea and main bronchus. Electrical field stimulation induced airway constriction in all three locations in M and IM groups. However, after administration of 10−6 M atropine and 10−6 M propranolol, electrical field stimulation-induced contraction was significantly smaller in the hilar bronchus of IM than M animals, and this difference was not prevented by pretreatment with 5 × 10−5 M indomethacin. Although radioimmunoassay showed no difference in the tissue content of substance P between M and IM airways, the constrictive responses to exogenous substance P and neurokinin A were markedly greater in M airways at all three locations. In conclusion, the constriction of isolated airways evoked by C-fiber stimulation was significantly weaker in the IM guinea pigs, probably because of a less potent effect of tachykinins on the airway smooth muscle.

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Multiple responses to electrical field stimulation in circular muscle of canine gastric corpus

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-152 ◽

1984 ◽

Vol 62 (8) ◽

pp. 912-918 ◽

Cited By ~ 8

Author(s):

Yasushi Sakai ◽

Edwin E. Daniel

Keyword(s):

Substance P ◽

Circular Muscle ◽

Electrical Field Stimulation ◽

Scorpion Venom ◽

Adrenergic Blockade ◽

Field Stimulation ◽

Electrical Field ◽

Gastric Corpus

Innervation of circular muscle of the canine stomach studied in vitro was investigated by subjecting muscle strips to electrical field stimulation. Strips were cut from the lesser curvature of the gastric corpus and stimulated with 10-s trains of 0.5-ms pulses at 0.5–20 Hz, 40 V. Most responses were classified into one of three types. In general, field stimulation tended to elicit sequences of varying magnitudes of transient on-contraction, on-relaxation, off-relaxation, off-contraction. Responses were abolished by tetrodotoxin. On-contraction was almost abolished by atropine plus desensitization by 5-hydroxytryptamine (5-HT) or substance P. On-relaxation and off-relaxation were not affected by adrenergic blockade, methysergide, apamin, or 4-aminopyridine. ATP usually caused contraction and slightly diminished relaxation to field stimulation. Vasoactive intestinal polypeptide (VIP) had little effect on tone and response to field stimulation. Relaxation disappeared after scorpion venom treatment. This probably resulted from depletion of the transmitter which mediates relaxation. Off-contraction was reduced by atropine, desensitization by 5-HT or substance P, cromoglycate, indomethacin or ATP, but was not affected by adrenergic blockade, hexamethonium, methysergide, mepyramine, or VIP. The findings suggest that innervation of gastric corpus circular muscle included excitatory cholinergic and both excitatory and inhibitory noncholinergic, nonadrenergic innervation. However, the responses of circular muscle to field stimulation in vitro were drastically different from those obtained previously in vivo, suggesting damage or altered inputs to circular muscle when strips of circular muscle are studied.

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Enkephalinase inhibitor potentiates substance P- and electrically induced contraction in ferret trachea

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.4.1401 ◽

1987 ◽

Vol 63 (4) ◽

pp. 1401-1405 ◽

Cited By ~ 92

Author(s):

K. Sekizawa ◽

J. Tamaoki ◽

J. A. Nadel ◽

D. B. Borson

Keyword(s):

Smooth Muscle ◽

Substance P ◽

Response Curve ◽

Electrical Field Stimulation ◽

Smooth Muscle Contraction ◽

Field Stimulation ◽

Electrical Field ◽

Contractile Responses ◽

Cholinergic Neurotransmission

To determine the role of endogenous enkephalinase (EC 3.4.24.11) in regulating peptide-induced contraction of airway smooth muscle, we studied the effect of the enkephalinase inhibitor, leucine-thiorphan (Leu-thiorphan), on responses of isolated ferret tracheal smooth muscle segments to substance P (SP) and to electrical field stimulation (EFS). Leu-thiorphan shifted the dose-response curve to SP to lower concentrations. Atropine or the SP antagonist [D-Pro2,D-Trp7,9]SP significantly inhibited SP-induced contractions in the presence of Leu-thiorphan. Leu-thiorphan increased the contractile responses to EFS dose dependently, an effect that was significantly inhibited by the SP antagonist [D-Pro2,D-Trp7,9]SP. SP, in a concentration that did not cause contraction, increased the contractile responses to EFS. This effect was augmented by Leu-thiorphan dose dependently and was not inhibited by hexamethonium or by phentolamine but was inhibited by atropine. Because contractile responses to acetylcholine were not significantly affected by SP or by Leu-thiorphan, the potentiating effects of SP were probably on presynaptic-postganglionic cholinergic neurotransmission. Captopril, bestatin, or leupeptin did not augment contractions, suggesting that enkephalinase was responsible for the effects. These results suggest that endogenous tachykinins modulate smooth muscle contraction and endogenous enkephalinase modulates contractions produced by endogenous or exogenous tachykinins and tachykinin-induced facilitation of cholinergic neurotransmission.

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Noradrenergic influence on epithelial responses of rabbit ileum to secretagogues

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.5.g919 ◽

1989 ◽

Vol 256 (5) ◽

pp. G919-G924 ◽

Cited By ~ 1

Author(s):

K. A. Hubel ◽

K. S. Renquist ◽

G. Varley

Keyword(s):

Vasoactive Intestinal Polypeptide ◽

Short Circuit ◽

Short Circuit Current ◽

Electrical Field Stimulation ◽

Field Stimulation ◽

Rabbit Ileum ◽

Electrical Field ◽

Physiological Importance ◽

Intrinsic Nerves ◽

Pm 10

Norepinephrine is one of three neurotransmitters that may act directly on enterocytes to enhance absorption; its interaction with secretagogues is of physiological importance. We have studied the influence of norepinephrine on the short-circuit current (Isc) responses to acetylcholine (ACh; 10 microM), vasoactive intestinal polypeptide (VIP; 100 pM-10 nM), peptide histidine isoleucine (PHI; 100 pM-10 nM), histamine (0.1 mM), and to electrical field stimulation (EFS) of rabbit ileum mounted in flux chambers. Tetrodotoxin reduced the response to norepinephrine (10 microM) by 40% and to histamine by 32% but did not affect responses to VIP or PHI. Norepinephrine decreased the ACh response (EC50, 70 nM) and reduced the responses to PHI (less than or equal to 87%), to EFS (less than or equal to 75%), and to histamine (less than or equal to 42%). Norepinephrine decreased the response to VIP (500 pM) but not to higher or lower VIP concentrations. It enhanced the response to VIP (10 nM) and to theophylline (5 mM). We conclude that 1) norepinephrine increases absorption by acting on nerves and enterocytes; 2) the failure of norepinephrine to reduce the Isc response to VIP when the VIP-induced increment in Isc is comparable to that caused by EFS is evidence that VIP does not mediate the EFS response; 3) PHI might mediate the EFS response; and 4) VIP, PHI, and histamine affect enterocytes directly; histamine also affects intrinsic nerves.

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