Inhibitory effects of pirenzepine on muscarinic stimulation of rat pancreas

The binding properties and pharmacological effects of pirenzepine were compared to those of atropine in isolated pancreatic acini and pancreatic membranes of rats. In the first preparation, pirenzepine and atropine blocked [N-methyl-3H]scopolamine ([3H]NMS) binding, pirenzepine being 110 times less potent than atropine (KD for pirenzepine 0.38 microM and for atropine 3.5 microM). A similar difference in potency was observed with respect to carbamylcholine stimulation of amylase secretion (IC50 for pirenzepine 4.5 microM and for atropine 30 nM) and calcium efflux (IC50 for pirenzepine 2.8 microM and for atropine 4 nM). Correspondingly, in rat pancreatic membranes, the KD values for pirenzepine and atropine were 250 and 1.5 nM, respectively. These data are compatible with the hypothesis that the in vitro antimuscarinic effect of pirenzepine on the rat pancreas is linked to the occupancy of a single homogeneous class of receptors with a low affinity for the antagonist.SCOPUS: ar.j