Abstract
Administration of E. coli endotoxin (1 mg kg−1, i.v.) abolished the acid response induced by the i.v. infusion of pentagastrin (8 μg kg−1, h-1) in the continuously perfused stomach of the anaesthetized rat. Local serosal application of tetrodotoxin (36 ng per rat) completely restored acid responses to pentagastrin in endotoxin-treated rats. However, pretreatment with atropine (0.5 mg kg−1, s.c.), capsaicin (20, 30, and 50 mg kg−1, s.c. 2 weeks before the study) or guanethidine (16 mg kg−1, s.c. 3 and 16h before) did not influence the inhibitory effects of endotoxin. Continuous i.v. infusion with NG-nitro arginine methyl ester (L-NAME, 10 mg kg−1, h−1) restored the secretory responses to pentagastrin in endotoxin treated rats. The effects of L-NAME were reversed by L-arginine (100 mg kg−1, h−1, i.v.), but not by its enantiomer D-arginine (100 mg kg−1, h−1, i.v.). The secretory responses elicited by pentagastrin (10−10–10−6 M) in the isolated lumen perfused stomach of the rat were not influenced by incubation (100 min) with endotoxin (10 μg ml −1). These observations with tetrodotoxin indicate that inhibition of acid secretion by endotoxin in vivo involves neuronal activity, while inhibition of NO synthesis had a comparable inhibitory action. Activation of a systemic non-adrenergic non-cholinergic neuronal pathway involving NO could thus mediate the acute acid inhibitory effects of endotoxin.
Similar content being viewed by others
References
Barrachina MD, Martinez-Cuesta MA, Canct A, Esplugues JV, Esplugues J (1992) Effects of local gastric capsaicin on distension-stimulated acid secretion. Naunyn-Schmiedebergs Arch Pharmacol 346:685–690
Boughton-Smith NK, Whittle BJR (1981) The gastric antisecretory actions of prostaglandin E2 and stable prostacyclin analogues against different secretagogues in perfused whole-stomachs of rat and mouse in vitro. Br J Pharmacol 72:291–298
Bredt DS, Hwang PM, Snyder SH (1990) Localization of nitric oxide synthase indicating a neuronal role for nitric oxide. Nature 347:768–770
Desai KM, Sessa WC, Vane JR (1991) Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature 351:477–479
Esplugues JV, Barrachina MD, Calatayud S, Pique JM, Whittle BJR (1993) Nitric oxide mediates the inhibition by interleukin-1ß of pentagastrin-stimulated rat gastric acid secretion. Br J Pharmacol 108:9–10
Holzer P (1991) Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmac Rev 43:143–201
Knowles RG, Palacios M, Palmer RMJ, Moncada S (1989) Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for the stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci USA 86:5159–5162
Li CG, Rand MJ (1990) Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus. Eur J Pharmacol 191:303–309
Martinez-Cuesta MA, Barrachina MD, Pique JM, Whittle BJR, Esplugues JV (1992) The role of nitric oxide and platelet-activating factor in the inhibition by endotoxin of pentagastrin-stimulated gastric acid secretion. Eur J Pharmacol 218:351–354
Moncada S (1992) The l-arginine - nitric oxide pathway. Acta Physiol Scand 145:201–227
Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmac Rev 43:109–142
Pique JM, Esplugues JV, Whittle BJR (1990) Influence of morphine or capsaicin pretreatment on rat gastric microcirculatory response to PAF. Am J Physiol 258:G352-G357
Pique JM, Esplugues JV, Whittle BJR (1992) Endogenous nitric oxide as a mediator of gastric mucosal vasodilatation during pentagastrin-stimulated acid secretion in the rat. Gastroenterology 102:168–174
Radomski MW, Palmer RMJ, Moncada S (1990) Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 87:10043–10047
Rees DD, Palmer RJM, Schulz R, Hodson HF, Moncada S (1990) Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol 101:746–752
Sanders KM, Ward SM (1992) Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 25: G379-G392
Snyder SH (1992) Nitric oxide: first in a new class of neurotransmitters?. Science 257:494–496
Whittle BJR (1993) Neuronal and endothelium-derived mediators in the modulation of the gastric microcirculation: integrity in the balance. Br J Pharmacol 110:3–17
Whittle BJR, Lopez-Belmonte J, Moncada S (1990) Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and neuropeptides in the rat. Br J Pharmacol 99: 607–611
Author information
Authors and Affiliations
Additional information
Correspondence to: J. V. Esplugues at the above address
Rights and permissions
About this article
Cite this article
Martinez-Cuesta, M.A., Barrachina, M.D., Whittle, B.J.R. et al. Involvement of neuronal processes and nitric oxide in the inhibition by endotoxin of pentagastrin-stimulated sastric acid secretion. Naunyn-Schmiedeberg's Arch Pharmacol 349, 523–527 (1994). https://doi.org/10.1007/BF00169142
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169142