AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 3 553-G566, Copyright © 1992 by American Physiological Society

ARTICLES

Identification and localization of 5-HT1P receptors in the guinea pig pancreas

A. L. Kirchgessner, M. T. Liu, H. Tamir and M. D. Gershon
Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032.

Enteropancreatic 5-hydroxytryptamine (5-HT)-immunoreactive nerve fibers have recently been described. To test the hypothesis that pancreas contains 5-HT receptors similar to those that characterize the enteric nervous system, binding of 5-[3H]HT to pancreatic membranes was investigated. Membranes were prepared by differential centrifugation from guinea pig pancreas, and binding of 5-[3H]HT was measured by use of a rapid filtration assay. Alternatively, 5-[3H]HT-binding sites were analyzed and located by radioautography on frozen sections of unfixed pancreas. The 5-HT1P receptor-specific antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), was used to define nonspecific binding in all assays. High-affinity reversible binding of 5-[3H]HT to pancreatic membranes was found. Good agreement was observed when Kd was determined from saturation isotherms (Kd = 2.1 +/- 0.4 nM; Bmax = 0.6 +/- 0.07 pmol/mg protein) or from the ratio of association and dissociation constants (2.7 +/- 0.04 nM). As is true of 5-[3H]HT binding to enteric 5-HT1P receptors, binding of 5-[3H]HT to pancreatic membranes was inhibited by 5-HTP-DP, 5- and 6-hydroxyindalpine (agonists at 5-HT1P receptors), and guanine nucleotides. In contrast, binding of 5-[3H]HT to pancreatic membranes was not inhibited by a variety of compounds known to bind to other types of 5-HT receptor, to the neuronal 5-HT transporter, to alpha- or beta-adrenoceptors, or to dopamine receptors. We concluded that pancreas contains 5-HT1P receptors with properties similar to those of bowel. Radioautography and immunocytochemistry with an anti-idiotypic antibody that recognizes 5-HT receptors revealed that pancreatic 5-HT1P receptors (identified with appropriate inhibitors of 5-[3H]HT or antibody binding) were concentrated in ganglia, nerves, and unidentified cells in both exocrine and endocrine pancreas. These observations suggest that future studies of 5-HT's role in pancreatic physiology should concentrate on enteropancreatic innervation and 5-HT1P receptors.

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