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Am J Physiol Gastrointest Liver Physiol 277: G469-G477, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 2, G469-G477, August 1999

Electrical physiological evidence for highand low-affinity vagal CCK-A receptors

Ying Li, Jinxia Zhu, and Chung Owyang

Gastroenterology Research Unit, Department of Internal Medicine, The University of Michigan Health System, Ann Arbor, Michigan 48109-0362

We have demonstrated that under physiological conditions CCK acts through vagal high-affinity CCK-A receptors to mediate pancreatic secretion. In this study, we evaluated the vagal afferent response to endogenous CCK in rats and defined the CCK-receptor affinity states and the vagal-receptive field responsive to CCK stimulation using electrophysiological studies. Experiments were performed on anesthetized rats prepared with bile-pancreatic fistula. Plasma CCK levels were elevated by diverting bile-pancreatic juice (BPJ). The single-unit discharge of sensory neurons supplying the gastrointestinal tract was recorded from the nodose ganglia. All units studied were either silent or they had a very low resting discharge frequency. Thirty-two single units were studied extensively; seven were shown to be stimulated by diversion of BPJ (2.6 ± 2 impulses/min at basal to 40 ± 12 impulses/min after diversion). Acute subdiaphragmatic vagotomy or perivagal capsaicin treatment abolished the response. The CCK-A-receptor antagonist CR-1409, but not the CCK-B antagonist L-365260, blocked the vagal response to endogenous CCK stimulation. Infusion of the low-affinity CCK-receptor antagonist CCK-JMV-180 completely blocked the vagal afferent response to the diversion of BPJ in three of seven rats tested but had no effect on the response in the remaining four. In a separate study, we demonstrated that gastric, celiac, or hepatic branch vagotomy abolished the response in different subgroups of neurons. In conclusion, under physiological conditions, CCK acts on both high- and low-affinity CCK-A receptors present on distinct vagal afferent fibers. The vagal CCK-receptor field includes the regions innervated by the gastric, celiac, and hepatic vagal branches. This study provides electrophysiological evidence that vagal CCK receptors are present on the vagal gastric, celiac, and hepatic branches and may occur in high- and low-affinity states.

nodose ganglia; cholecystokinin-JMV-180; selective branch vagotomy


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