Increase in the amount of adenylate cyclase in rat gastrocnemius muscle after denervation

Abstract

After section of the sciatic nerve, the basal adenylate cyclase (AC) activity in rat gastrocnemius muscle increased 6–7 times per membrane protein and about 2 times per whole muscle in the following 30 or 40 days. The AC activity in the muscle 30 days after denervation was increased about 4 times by folskolin. Calcitonin gene-related peptide (CGRP) also increased the adenylate cyclase activity in the denervated muscle. The binding of [ 3H]-forskolin (10nM) to cells isolated from gastrocnemius muscle was examined to determine the amount of AC molecules. Inhibition of [ 3H]-forskolin binding by increasing amounts of unlabeled forskolin gave a sigmoid curve with a IC 50 value of 3×10 −7 M. Results showed that the number of [ 3H]-forskolin binding sites per cell was higher on the denervated side than on the control side, like the basal AC activity. The IC 50 values for inhibition by unlabeled forskolin of binding of [ 3H]-forskolin were similar to muscles on the control and denervated sides. These results suggest that an increase in the AC activity induced by denervation was due to an increase in the numbers of AC molecules in the muscle.