Biochemical and pharmacological characteristics of muscarinic choliner
gic receptors in isolated guinea pig pancreatic ducts were determined
in the present study. Duct homogenates bound 6.82 +/- 0.69 fmol of H-
3!N-methylscopolamine (H-3!NMS)/mug of DNA with a K(d) of 0.73 +/- 0.
05 nM. The density of H-3!NMS binding sites in the excretory ducts wa
s seven times greater than that in acini from the same pancreases. Com
petition binding studies with atropine, pirenzepine, -piperidinyl!acet
yl!-5,11-dihydro-6H-pyrido2,3-b! 1,4!benzodiazepine-6-one (AF-DX 116
), and 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP) indic
ated that both M2 and M3 subtypes of muscarinic receptors are present
in these preparations of isolated pancreatic ducts. Electrophoretic an
alysis of H-3!propylbenzilylcholine mustard-labeled unreduced and red
uced duct muscarinic receptors provided molecular mass estimates of 62
.6 +/- 2.5 and 58.0 +/- 1.6 kDa, respectively. Deglycosylation of duct
al muscarinic receptors with N-glycanase decreased their apparent mole
cular mass by approximately 4 kDa. These results demonstrate that isol
ated pancreatic ducts express both M2 and M3 muscarinic receptors, wit
h the former subtype predominating.