Effects of Pyridoxal 5′-Phosphate on Synaptic Transmission in Smooth Muscle

Abstract

We studied the influence of the vitamin B6 form most extensively distributed in the organism, pyridoxal 5′-phosphate (PyrP), on neuromuscular transmission in the smooth muscle of the circular layer of the guinea pig distal colon and of the ileum and an initial segment of the jejunum of humans. Application of 10-10 to 10-3 M PyrP reversibly and in a dose-dependent manner decreased the amplitude of non-cholinergic non-adrenergic inhibitory synaptic potentials (ISP) and increased their duration. Under the influence of 10-8 to 10-4 M PyrP, both the amplitude and duration of ATP- and noradrenaline-induced hyperpolarizations increased. Application of 10-4 M PyrP completely suppressed the sensitivity of smooth muscle cells to noradrenaline, but a hyperpolarizing effect of exogenous ATP was preserved. The PyrP-induced amplitude decrease and prolongation of ISP were preserved in the presence of 10-4 M hexonium (a ganglioblocker), 5 · 10-7 M apamin (a blocker of Ca2+-dependent K+ channels of small conductance), 10-5 M verapamil (a blocker of L-type Ca2+ channels), and 10-4 M Nω-nitro-L-arginine (a blocker of NO-synthase). It seems probable that a decrease in the ISP amplitude is related to a presynaptic PyrP effect. Under conditions of PyrP-induced suppression of non-cholinergic non-adrenergic inhibition, non-cholinergic short-latency excitatory synaptic potentials could be recorded in smooth muscle. Thus, PyrP is an effective modulator of synaptic transmission in smooth muscle of the gastrointestinal tract of mammals.