Endogenous nitric oxide release modulates the direction and frequency of colonic migrating motor complexes in the isolated mouse colon

Spontaneous colonic migrating motor complexes (CMMCs) were recorded from circular muscle at three sites along the isolated mouse colon. The interval between CMMCs was decreased from similar to3 min in control solution, by similar to 55% in a nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine (L-NNA; 100 mu mol L-1). This was associated with a shift in migration direction of CMMCs, such that CMMCs migrated in an oral direction. Application of the endogenous substrate for NOS, L-arginine, at a low concentration used to mimic plasma concentration (134 mu mol L-1), or a high concentration (5 mmol L-1) suppressed CMMCs (for at least 15 min) which were replaced by high frequency (10-15 min(-1)), short duration (half width similar to1.5 s) contractions of variable amplitudes (largest in the proximal region) until CMMCs resumed. CMMCs remained in the presence of D-arginine (134 mu mol L-1 and 5 mmol L-1). Apamin (250 nmol L-1) did not alter the interval between CMMCs, however, additional nonmigrating contractions were observed between the CMMCs in the distal region. In addition to its effects on smooth muscle tone, NO, but not apamin-sensitive channels, plays an important role in suppressing the frequency of migrating contractions in the isolated mouse colon. Consideration should be given to the inclusion of L-arginine, in in vitro experiments where there may be spontaneous activity in NOS containing neurones.