Choline&c Stimulation of Skeletal Muscle Alanine and Glutamine Formation and Release

The mechanism of cholinergic stimulation of alanine and glutamine formation and release from skeletal muscle was studied using rat epitrochlaris preparations. The increased alanine and glutamine release produced by carbamylcholine (10e6 M) was reproduced by tetramethylammonium (10m6 M) but not by pilocarpine (10m6 M) and was blocked by hexamethonium (10m4 M) but not by atropine (10e7 M). This increased alanine and glutamine release was not associated with altered muscle CAMP levels. However, carbamylcholine (10e6 M) and tetramethylammonium (10m6 M) did increase levels of cGMP, 134% and lOl%, respectively, and these increments in cGMP were blocked by hexamethonium but not by atropine. Carbamylcholine produced a concentration-dependent increase in cGMP levels. Methylisobutylxanthine and theophylline augmented the increased amino acid release and increased cGMP levels produced by carbamylcholine. Neither xanthine derivative alone altered alanine and glutamine release or cyclic nucleotide levels. Added cGMP increased amino acid release and the uptake of [U-‘4C]alanine and (Yamino[‘4C]isobutyric acid. Carbamylcholine did not alter muscle phosphorylase a activity, glycogen levels, or basal adenylate cyclase activity. These data indicate that choline&c stimulation of muscle alanine and glutamine formation and release involves a nicotinic cholinergic receptor and may be mediated by increased levels of cGMP, which in turn may result from a cholinergic stimulation of muscle guanylyl cyclase.