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Differentiation of Muscarinic Cholinergic Receptors in Acinar Carcinoma of Rat Pancreas¹

Department of Pathology, Northwestern University Medical School [J. L. C., J. R. W.], and the Microbiology Laboratories, Veterans Administration Lakeside Medical Center [J. R. W.], Chicago, Illinois 60611

Analysis of muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat by measurement of N-[methyl-³H]scopolamine binding has revealed a single homogenous population of muscarinic receptors in the tumor. The plasmalemma density (25 receptors/µm² of cell membrane surface) and dissociation constant (0.4 nM of muscarinic receptors in acinar carcinoma cells are identical to the density and affinity of muscarinic receptors in normal acinar cells of rat pancreas. Muscarinic receptors in the carcinoma are functionally linked to cholinergic stimulation of cellular Ca²⁺ release. An equivalent number of functional muscarinic receptors is present in poorly differentiated carcinoma cells which are deficient in zymogen granules and protein secretion, as compared to well-differentiated carcinoma cells which contain granules and secrete protein in response to cholinergic stimulation. These observations indicate that muscarinic cholinergic receptors are displayed in normal fashion on tumor membranes and are fully expressed in carcinoma cells regardless of their degree of secretory development. Expression of muscarinic cholinergic receptors is thus a stable phenotypic property of pancreatic acinar carcinoma cells. This suggests that muscarinic receptor maturation is an early event in the differentiation of pancreatic exocrine cells, preceding acquisition of secretory responsiveness to cholinergic stimulation.

¹ This investigation was supported by USPHS Grant CA 27443 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at the Department of Pathology, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611.

Received 4/ 9/85. Revised 7/ 2/85. Accepted 7/ 5/85.

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