Effects and underlying mechanisms of _L-arginine on spontaneous muscle contraction of rat colon

Arginine (Arg), as a basic amino acid, has been reported to be involved in regulation of gut motility. However, the evidence is limited and the underlying mechanism is not fully understood. Our study was conducted to investigate the effects of _L-Arg on spontaneous contraction of the longitudinal muscle strip (LMS) of the rat colon and the relevant mechanisms. An organ bath system was used to detect the contractile force of the LMS. Whole-cell voltage-clamp techniques were applied to observe alterations in the currents of large conductance Ca²⁺-activated K⁺ (K_Ca) channels, voltage-dependent potassium (K_V) channels, and L-type Ca²⁺ channels (LTCCs) in smooth muscle cells (SMCs) of the colon. We found that _L-Arg within the physiological concentration had no effect on contraction of LMS, while 1 mM _L-Arg significantly increased both the amplitude and frequency of LMS contractility. And the increase in force was mucosa-dependent, whereas changes in frequency as well as in amplitude were inhibited by atropine. In addition, _L-Arg (1 mM) activated the LTTCs and inhibited both K_Ca channels and K_V channels on SMCs. Thus, _L-Arg above the physiological concentration exerted an excitatory effect on colonic LM contraction, and stimulation by _L-Arg was mediated by ACh. In addition, LTCCs, K_Ca channels, and K_V channels on SMCs were involved in the action of _L-Arg.