Nitric Oxide, and Not Vasoactive Intestinal Peptide, As the Main Neurotransmitter of Vagally Induced Relaxation of the Guinea Pig Stomach

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1994 Dec 1

PMID 7534182

Citations 18

Authors

K M Desai

T D Warner

A E Bishop

J M Polak

J R Vane

Affiliations

Soon will be listed here.

Abstract

1. Nitric oxide synthase (NOS) was localized in the guinea pig stomach by immunocytochemistry. In vitro experiments were carried out on the isolated stomach of the guinea pig to study any possible links between nitric oxide (NO) and vasoactive intestinal peptide (VIP) in mediating relaxations induced by vagal stimulation. 2. NOS was localized to nerve cell bodies and nerve fibre varicosities of the myenteric plexus in wholemounts of the longitudinal muscle-myenteric plexus of the stomach fundus. The NOS-positive cells had a Dogiel type I morphology characteristic of motor neurones. 3. The cross-sections of the stomach wall showed NOS-positive neurones mainly in the myenteric plexus ganglia and NOS-positive nerve fibre varicosities in the circular muscle layer. 4. Relaxations induced by vagal stimulation were almost completely prevented by L-NAME with an IC50 value of 5.5 x 10(-6) M. This inhibition was reversed by L-arginine (2 mM). 5. VIP (100 nM) induced reproducible relaxations of the stomach. These were unaffected by tetrodotoxin (2 microM) or N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). 6. Desensitization to the relaxant effect of VIP partially reduced relaxations induced by vagal stimulation, glyceryl trinitrate or sodium nitroprusside but not noradrenaline. 7. These results show that NO has a neuronal origin in the guinea pig stomach, and support NO, and not VIP, as the major neurotransmitter of vagally induced gastric relaxation in the guinea pig.

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References

GRAHAM Jr R, Karnovsky M . The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966; 14(4):291-302. DOI: 10.1177/14.4.291. View

Bredt D, Hwang P, Snyder S . Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990; 347(6295):768-70. DOI: 10.1038/347768a0. View

Costa M, Buffa R, Furness J, Solcia E . Immunohistochemical localization of polypeptides in peripheral autonomic nerves using whole mount preparations. Histochemistry. 1980; 65(2):157-65. DOI: 10.1007/BF00493164. View

Bitar K, Makhlouf G . Relaxation of isolated gastric smooth muscle cells by vasoactive intestinal peptide. Science. 1982; 216(4545):531-3. DOI: 10.1126/science.6176025. View

Grider J, Cable M, Said S, Makhlouf G . Vasoactive intestinal peptide as a neural mediator of gastric relaxation. Am J Physiol. 1985; 248(1 Pt 1):G73-8. DOI: 10.1152/ajpgi.1985.248.1.G73. View

Gulbenkian S, Wharton J, Polak J . The visualisation of cardiovascular innervation in the guinea pig using an antiserum to protein gene product 9.5 (PGP 9.5). J Auton Nerv Syst. 1987; 18(3):235-47. DOI: 10.1016/0165-1838(87)90122-6. View

Palmer R, Ferrige A, Moncada S . Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987; 327(6122):524-6. DOI: 10.1038/327524a0. View

Damato M, De Beurme F, Lefebvre R . Comparison of the effect of vasoactive intestinal polypeptide and non-adrenergic non-cholinergic neurone stimulation in the cat gastric fundus. Eur J Pharmacol. 1988; 152(1-2):71-82. DOI: 10.1016/0014-2999(88)90837-0. View

De Beurme F, Lefebvre R . Vasoactive intestinal polypeptide as possible mediator of relaxation in the rat gastric fundus. J Pharm Pharmacol. 1988; 40(10):711-5. DOI: 10.1111/j.2042-7158.1988.tb07000.x. View

10.

Li C, Rand M . Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus. Eur J Pharmacol. 1990; 191(3):303-9. DOI: 10.1016/0014-2999(90)94162-q. View

11.

Dwyer M, Bredt D, Snyder S . Nitric oxide synthase: irreversible inhibition by L-NG-nitroarginine in brain in vitro and in vivo. Biochem Biophys Res Commun. 1991; 176(3):1136-41. DOI: 10.1016/0006-291x(91)90403-t. View

12.

Li C, Rand M . Evidence that part of the NANC relaxant response of guinea-pig trachea to electrical field stimulation is mediated by nitric oxide. Br J Pharmacol. 1991; 102(1):91-4. PMC: 1917893. DOI: 10.1111/j.1476-5381.1991.tb12137.x. View

13.

Desai K, Sessa W, Vane J . Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature. 1991; 351(6326):477-9. DOI: 10.1038/351477a0. View

14.

Noack E, Feelisch M . Molecular mechanisms of nitrovasodilator bioactivation. Basic Res Cardiol. 1991; 86 Suppl 2:37-50. DOI: 10.1007/978-3-642-72461-9_5. View

15.

Desai K, Zembowicz A, Sessa W, Vane J . Nitroxergic nerves mediate vagally induced relaxation in the isolated stomach of the guinea pig. Proc Natl Acad Sci U S A. 1991; 88(24):11490-4. PMC: 53161. DOI: 10.1073/pnas.88.24.11490. View

16.

Grider J, Murthy K, Jin J, Makhlouf G . Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol. 1992; 262(4 Pt 1):G774-8. DOI: 10.1152/ajpgi.1992.262.4.G774. View

17.

Belvisi M, Stretton C, Yacoub M, Barnes P . Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in humans. Eur J Pharmacol. 1992; 210(2):221-2. DOI: 10.1016/0014-2999(92)90676-u. View

18.

Llewellyn-Smith I, Song Z, Costa M, Bredt D, Snyder S . Ultrastructural localization of nitric oxide synthase immunoreactivity in guinea-pig enteric neurons. Brain Res. 1992; 577(2):337-42. DOI: 10.1016/0006-8993(92)90294-j. View

19.

Damato M, Curro D, Montuschi P, Ciabattoni G, Ragazzoni E, Lefebvre R . Release of vasoactive intestinal polypeptide from the rat gastric fundus. Br J Pharmacol. 1992; 105(3):691-5. PMC: 1908460. DOI: 10.1111/j.1476-5381.1992.tb09040.x. View

20.

Lefebvre R, Baert E, Barbier A . Influence of NG-nitro-L-arginine on non-adrenergic non-cholinergic relaxation in the guinea-pig gastric fundus. Br J Pharmacol. 1992; 106(1):173-9. PMC: 1907451. DOI: 10.1111/j.1476-5381.1992.tb14311.x. View