Cholinergic stimulation of skeletal muscle alanine and glutamine formation and release. Evidence for mediation by a nicotinic cholinergic receptor and guanosine 3':5'-monophosphate.
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 (10(-6) M) was reproduced by tetramethylammonium (10(-6) M) but not by pilocarpine (10(-6) M) and was blocked by hexamethonium (10(-4) M) but not by atropine (10(-7) M). This increased alanine and glutamine release was not associated with altered muscle cAMP levels. However, carbamylcholine (10(-6) M) and tetramethylammonium (10(-6) M) did not increase levels of cGMP, 134% and 101%, 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-14C]alanine and alpha-amino[14C]isobutyric acid. Carbamylcholine did not alter muscle phosphorylase a activity, glycogen levels, or basal adenylate cyclase activity. These data indicate that cholinergic 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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000409:Alanine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D006584:Hexamethonium Compounds; D000644:Quaternary Ammonium Compounds; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D010862:Pilocarpine; D005973:Glutamine; D001285:Atropine; D002217:Carbachol; D013806:Theophylline; D000242:Cyclic AMP; D006005:Phosphorylases; C027917:tetramethylammonium; D006152:Cyclic GMP; D000409:Alanine; D015056:1-Methyl-3-isobutylxanthine