A CHOLINERGIC ANTAGONIST IDENTIFIES A SUBCLASS OF MUSCARINIC RECEPTORS IN ISOLATED RAT PANCREATIC ACINI

  • 1 January 1987
    • journal article
    • research article
    • Vol. 240  (1) , 118-122
Abstract
Atropine, pirenzepine (PZ) and the novel antimuscarinic drug [11-[[2-(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116) were used to subclassify the pancreatic muscarinic receptor by correlating their effects on carbachol-mediated amylase release with their actions on the binding of [3H]N-methylscopolamine in rat pancreatic acini. Maximal stimulation of amylase release occurred at 3 .mu.M carbachol. Atropine, PZ and AF-DX 116 inhibited carbachol-mediated amylase release with the following pA2 values: atropine = 9.1, PZ = 6.5 and AF-DX 116 = 57. There was parallel inhibition of [3H]N-methylscopolamine binding, with the following inhibition constants: atropine = 2.38 nM, PZ = 426 nM and AF-DX 116 = 3660 nM. Using the same animals, these compounds inhibited [3H]N-methylscopolamine binding in homogenates from both cerebral cortex and heart. The order of potency was the same in the cerebral cortex as in the pancreas: atropine = 0.67 nM, PZ = 85 nM and AF-DX 116 = 440 nM. However, the heart had a significantly higher affinity for AF-DX 116. These findings suggest that the pancreatic acinar cell exhibits a distinct subclass of muscarinic M2 receptors that have a low affinity for AF-DX 116.