Garber A J, Entman M L, Birnbaumer L
J Biol Chem. 1978 Nov 10;253(21):7924-30.
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.
利用大鼠肱三头肌制备物研究了胆碱能刺激丙氨酸和谷氨酰胺从骨骼肌形成和释放的机制。氨甲酰胆碱（10⁻⁶ M）引起的丙氨酸和谷氨酰胺释放增加可被四甲基铵（10⁻⁶ M）重现，但不能被毛果芸香碱（10⁻⁶ M）重现，且被六甲铵（10⁻⁴ M）阻断，但不被阿托品（10⁻⁷ M）阻断。这种丙氨酸和谷氨酰胺释放增加与肌肉环磷酸腺苷（cAMP）水平改变无关。然而，氨甲酰胆碱（10⁻⁶ M）和四甲基铵（10⁻⁶ M）分别使环磷酸鸟苷（cGMP）水平升高134%和101%，且这些cGMP的升高被六甲铵阻断，但不被阿托品阻断。氨甲酰胆碱使cGMP水平呈浓度依赖性增加。甲基异丁基黄嘌呤和茶碱增强了氨甲酰胆碱引起的氨基酸释放增加和cGMP水平升高。单独使用这两种黄嘌呤衍生物均未改变丙氨酸和谷氨酰胺释放或环核苷酸水平。添加的cGMP增加了氨基酸释放以及[U-¹⁴C]丙氨酸和α-氨基[¹⁴C]异丁酸的摄取。氨甲酰胆碱未改变肌肉磷酸化酶a活性、糖原水平或基础腺苷酸环化酶活性。这些数据表明，胆碱能刺激肌肉丙氨酸和谷氨酰胺的形成和释放涉及烟碱型胆碱能受体，可能由cGMP水平升高介导，而cGMP水平升高反过来可能是由于胆碱能刺激肌肉鸟苷酸环化酶所致。
