Binding characteristics of the muscarinic receptor subtype in rabbit pancreas

The muscarinic receptor in the rabbit pancreas was characterized with the use of the labeled ligand (3H)-(-)-quinuclidinyl-benzylate ((3H)-(-)-QNB). Specific binding of (3H)-(-)-QNB to pancreatic acini was found to be reversible and of high affinity, with an equilibrium dissociation constant (KD) of 68 pmol/l and a receptor density (RT) of 170 fmol/mg protein. Agonist binding behaviour was investigated by displacement of (3H)-(-)-QNB binding by eight agonists like arecoline, arecaïdine-propargylester (APE) and carbachol, yielding only low affinity binding sites. The inhibition of (3H)-(-)-QNB binding by the selective antagonists pirenzepine, hexahydrosiladifenidol (HHSiD) and (11-[2-[diethyl-amino)-methyl)-1-piperidinyl]acetyl)-5,11-dihydro-6H-pyr ido (2,3-b) (1,4) benzodiazepin-6-one) (AF-DX 116) confirmed the M3 nature of the rabbit pancreatic receptor.