Muscarinic receptors in isolated guinea pig pancreatic ducts.

Biochemical and pharmacological characteristics of muscarinic cholinergic receptors in isolated guinea pig pancreatic ducts were determined in the present study. Duct homogenates bound 6.82 +/- 0.69 fmol of [3H]N-methylscopolamine ([3H]NMS)/micrograms of DNA with a Kd of 0.73 +/- 0.05 nM. The density of [3H]NMS binding sites in the excretory ducts was seven times greater than that in acini from the same pancreases. Competition binding studies with atropine, pirenzepine, 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b] [1,4]benzodiazepine-6-one (AF-DX 116), and 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP) indicated that both M2 and M3 subtypes of muscarinic receptors are present in these preparations of isolated pancreatic ducts. Electrophoretic analysis of [3H]propylbenzilylcholine mustard-labeled unreduced and reduced duct muscarinic receptors provided molecular mass estimates of 62.6 +/- 2.5 and 58.0 +/- 1.6 kDa, respectively. Deglycosylation of ductal muscarinic receptors with N-glycanase decreased their apparent molecular mass by approximately 4 kDa. These results demonstrate that isolated pancreatic ducts express both M2 and M3 muscarinic receptors, with the former subtype predominating.