The vagal nerves and peptides in the control of extrahepatic biliary motility. An experimental study in the cat.
An in vivo model for the simultaneous study of the motility of the gallbladder, sphincter of Oddi and duodenal wall in the anesthetized cat was developed. Changes in gallbladder volume were recorded as well as changes in the outflow from the sphincter of Oddi and from a vein graft inserted through the duodenal wall during perfusion at constant pressure. The distribution of three peptide hormones (substance P-SP, vasoactive intestinal peptide-VIP and cholecystokinin-CCK) within the feline extrahepatic biliary tree was studied immunocytochemically. Nerve terminals with SP-like immunoreactivity (LI) were distributed to the smooth muscle layers and also to acetylcholinesterase-positive ganglions cells in the intrinsic plexa. SP-LI was further demonstrated in cell bodies of the intrinsic plexa as well as in vagal axons. VIP-LI had a similar distribution. An especially rich VIP-ergic innervation was observed within the circular muscle layer of the sphincter of Oddi. SP-LI or VIP-LI did not occur in mucosal endocrine cells. On the other hand, CCK-LI was not demonstrated in nerves but occurred regularly in endocrine cells of the duodenal mucosa. Regional administration of SP elicited dose-dependent contractile motor effects on the biliary tree, which were not dependent on muscarinic or nicotinic cholinoceptors, but were inhibited by infusion of an antagonistic SP analogue indicating a direct effect on the smooth muscle cell. Efferent electrical vagal nerve stimulation elicited contractile motor responses, which were blocked by either atropine or infusion of the SP-analogue, indicating activation of a postganglionic cholinergic neuron via intrinsic or extrinsic SP neurons. These observation correlate well with the presence of SP nerve terminals on acetylcholinesterase-positive ganglion cells of the intrinsic plexa and SP axons within the vagus. An afferent mechanism cannot be excluded; antidromic activation of SP-containing axon collaterals from vagal afferents might act on intrinsic cholinergic neurons. The cellbodies of such afferents may be present in intrinsic plexa or within the sensory vagal nodose ganglion. VIP elicited relaxatory motor responses from the extrahepatic biliary tree, not influenced by blockade of cholinoceptors or beta-adrenoceptors. Stimulation of beta-adrenoceptors, or selective stimulation of beta 2-adrenoceptors caused dose-dependent relaxatory motor responses, which were antagonized by specific blockade. Stimulation of beta-adrenoceptors following selective blockade of beta 2-adrenoceptors resulted in relaxation, most probably mediated by beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Surgery I, University of Göteborg.
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Dahlstrand
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001659:Biliary Tract / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D002766:Cholecystokinin / Q000032:analysis / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009068:Movement / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D013268:Stimulation, Chemical; D013373:Substance P / Q000032:analysis / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D001285:Atropine; D002766:Cholecystokinin; D011433:Propranolol; D012844:Sincalide