Evidence That Muscarinic Receptors in Islet Cells are Not Coupled Functionally to Adenylate Cyclase Through the Inhibitory Guanine Nucleotide Binding Protein (Ni)

Summary

The effect of muscarinic agonist on adenylate cyclase was investigated in neonatal islet cells and in a clonal pituitary cell line (GH₄C₁) following labelling of the intracellular ATP pool with [2, 8³H]adenine. In islet cells carbamylcholine was without effect on basal or glucagon-stimulated adenylate cyclase activity, measured as ³H cyclic AMP production, but inhibited ³H cyclic AMP production in the clonal pituitary cells. The involvement of the inhibitory guanine nucleotide binding protein of adenylate cyclase (Ni) was investigated by the use of the Bordetella pertussis exotoxin, islet activating protein (IAP). Pre-treatment of islet cells with IAP was without effect on adenylate cyclase following carbamylcholine but in the clonal pituitary line abolished the inhibition of ³H cyclic AMP production. It is concluded that in the islet cell, in contrast to the clonal pituitary cell, muscarinic receptors are not effectively coupled through Ni to inhibit adenylate cyclase.

Key-Words

Adenylate Cyclase - Muscarinic Receptor - Pertussis Toxin - Pancreatic Islet - Clonal Pituitary Cell