Cholinergic dependence of gallbladder response to cholecystokinin in the guinea pig in vivo.
The physiological mechanism responsible for cholecystokinin (CCK)-induced gallbladder (GB) contraction is unclear. We investigated the relative roles of direct muscle stimulation and neural activation at physiological and supraphysiological levels of CCK-octapeptide (CCK-8) using an in vivo guinea pig model. GB pressure was measured by a pressure transducer inserted into the GB lumen. Infusion of CCK-8 (2.5-40 ng.kg-1.min-1) increased GB pressure in a dose-dependent fashion. Pretreatment with atropine or hexamethonium antagonized GB responses to low doses of CCK-8 (2.5-5 ng.kg-1.min-1) but had no effect on doses greater than 10 ng.kg-1.min-1. Bilateral truncal vagotomy also significantly reduced GB responses to low doses of CCK-8 (2.5-5 ng.kg-1.min-1) but did not affect responses to high doses (10-40 ng.kg-1.min-1). Atropine or hexamethonium had no further inhibitory effects on guinea pigs that had undergone truncal vagotomy. Fasted guinea pigs that were fed ad libitum produced a postprandial peak plasma CCK level of 7.8 +/- 1.8 pM. This level was most closely approximated by infusion of 5 ng.kg-1.min-1 of CCK-8 (8.4 +/- 2.6 pM). CCK-8 infusion at greater than or equal to 10 ng.kg-1.min-1 gave supraphysiological plasma CCK levels. These observations indicate that CCK stimulated GB contraction via both a neural and a direct smooth muscle effect. Doses of CCK-8 that produce physiological plasma CCK levels act via stimulation of presynaptic cholinergic neurons in a vagally mediated pathway, whereas doses of CCK-8 that produce supraphysiological CCK levels act directly on GB smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0362.
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Takahashi
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May
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Owyang
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects*; D006168:Guinea Pigs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction; D010275:Parasympathetic Nervous System / Q000502:physiology*; D015167:Vagotomy, Truncal
D006584:Hexamethonium Compounds; D018738:Hexamethonium; D001285:Atropine; D002766:Cholecystokinin