Nitric oxide as a nonadrenergic inhibitory transmitter in smooth muscle cells of the guinea pig gastro-intestinal tract: Mechanisms of action

The role of nitric oxide (NO) as a possible transmitter for nonadrenergic inhibitory transmission was studied on isolated muscle strips of the guinea pig gastro-intestinal tract (GIT) using sucrose-gap technique. In addition, the voltage clamp and intracellular dialysis techniques were employed to study the effects of sodium nitroprusside (NP) on isolated smooth muscle (SM) cells of thetaenia coli. N-nitro-L-arginine methyl ester (L-NAME), a blocker of NO synthesis from L-arginine (0.1 mM), was shown to selectively suppress the apamin-resistant component of nonadrenergic inhibitory junctional (synaptic) potentials (IJP) in the guinea pig GIT SM cells. At the same time, L-NAME did not affect the vasoactive intestinal polypeptide (VIP)- and NP-evoked hyperpolarization in SM cells of the colon. The NP-induced hyperpolarization (0.1 mM) was accompained by a decrease in the SM cell membrane resistance. Application of NP to isolated SM cells activated a small outward current and increased the frequency of spontaneous transient calcium-dependent outward currents. NP increased the Ca-dependent potassium current evoked in SM cells by step depolarization, but did not affect the potassium currents of delayed rectification. Our results suggest that NO is involved in generation of nonadrenergic IJP in SM cells of the guinea pig GIT. The action of NP on SM cells is complex and results in hyperpolarization and relaxation (partially through the activation of Ca-dependent potassium channels in SM cell membrane).