Vagal stimulation of rat exocrine pancreatic secretion occurs via multiple mediators.
BACKGROUND
The vagus nerve contains cholinergic and noncholinergic neurons that interact with peptidergic neurons of the enteric nervous system, which stain immunohistochemically for cholecystokinin, vasoactive intestinal polypeptide, and gastrin-releasing peptide.


METHODS
The role of these pancreatic exocrine secretagogues during electrical vagal stimulation was studied using specific inhibitors in urethane-anesthetized rats.


RESULTS
The pancreatic secretory response to vagal stimulation was blocked significantly by each of the following: the ganglionic blocker hexamethonium (100% inhibition); the muscarinic, cholinergic blocker atropine (85% inhibition); the specific cholecystokinin A-receptor antagonist L-364,718 (84% inhibition); a gastrin-releasing peptide-receptor blocker (91% inhibition); and a vasoactive intestinal polypeptide polyclonal antibody (89% inhibition). The response was not altered by a monoclonal antibody to somatostatin. A subthreshold dose of cholecystokinin octapeptide augmented the response to electrical vagal stimulation.


CONCLUSIONS
Suppression of tonic somatostatin release is not the final common event. The findings that subthreshold cholecystokinin augments vagal stimulation, together with marked inhibition by each antagonist used, are consistent with the hypothesis that potentiating interactions among several agonists mediate the vagal response in anesthetized rats. However, this study does not exclude acetylcholine as the final common mediator. Studies in conscious animals are needed to determine the physiological significance of these observations.
Nelson
M T
MT
Department of Surgery, University of California School of Medicine, San Francisco.
Debas
H T
HT
Mulvihill
S J
SJ
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001794:Blood Pressure; D020109:Devazepide; D004558:Electric Stimulation; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000502:physiology; D013004:Somatostatin / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D001570:Benzodiazepinones; D006584:Hexamethonium Compounds; D010276:Parasympatholytics; D011949:Receptors, Cholecystokinin; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D013004:Somatostatin; D020109:Devazepide