Mechanisms of non-adrenergic non-cholinergic synaptic transmission in smooth muscle cells of the gastrointestinal tract

Abstract

Non-adrenergic non-cholinergic (NANCh) inhibitory synaptic potentials in smooth muscle cells (SMC) of the gastrointestinal tract are of a complex transmitler and ion nature. A blocker of ATP receptors, suramin, blocks the fast component, while a blocker of NO synthase, L-NOARG, blocks the slow component of NANCh inhibitory synaptic potentials. In the presence of both suramin and L-NOARG, SMC respond to stimulation of the intramural plexus by generating a low-amplitude hyperpolarization, and VIP is likely to be the transmitter for this effect. Low-conductance Ca2*-dependent potassium channels are involved in generation of the fast component of NANCh inhibitory synaptic potentials, and these channels are effectively blocked by apamin. The slow component of this potential is generated by high-conductance Ca2+-depondent pota~ium channels. In the presence of both apamin and L-NOARG (or charibdotoxin), SMC respond to intramural stimulations with non-cholinergic excitatory synaptic potentials, and ATP application evokes depolarization. Both effects are blocked by suramin. In the presence of apamin, noradrenaline also evokes depolarization in SMC, and this effect, similarly to hyperpolarization under normal conditions, is blocked by phentolamine. Our studies allow us to suggest that in smooth muscles of the gastrointestinal tract there are two types of synaptic transmission: the excitatory cholinergic, adrenergic, and ATP-ergic transmission and the inhibitory adrenergic, ATP-ergic, NO-ergic, and VIP-ergic transmission.

Synaptic inhibition of smooth muscles of the human colon: Effects of vitamin B6 and its derivatives

“…Non-adrenergic synaptic inhibition in SMs of the circular layer of the distal portion of the guinea-pig colon has been studied in detail [2,3]. It is believed that ATP mediates generation of IJPs through activation of Р 2 purinoceptors [3].…”

“…Our data are indicative of rather significant speciesrelated properties of the course of processes of synaptic inhibition in SMs belonging to anatomically comparable parts of the human colon and guinea-pig colon. Based on our own data and on the existing concept on the involvement of a purinergic transmitter in the formation of the first fast component of IJPs generated in SMs of the guinea-pig colon [2,3], we studied the effect of PPh on IJPs recorded in MSs obtained from the colon of humans (for comparison) and guinea pigs. In our experiments, we used human MSs, which were obtained from the intestinal fragments localized at a distance of several tens of centimeters from the zone of the digestive tract affected by one disease or another.…”

“…It is believed that ATP mediates generation of IJPs through activation of Р 2 purinoceptors [3]. This is why we compared parameters of IJPs generated in MSs of the human sigmoid colon and of the topographically corresponding distal part of the guinea-pig colon (Table 3).…”

“…In various mammals, such inhibition possesses distinct species-dependent properties [2][3][4][5]. Elucidation of the mechanisms underlying non-adrenergic inhibition of SMs of the human intestine is complicated by the fact that researchers used rather heterogeneous resection materials obtained from patients with different pathological changes in the digestive tract.…”

Membrane mechanisms of the effects of apamin on ion currents in smooth muscle cells

“…Later [3,4], it was found that these inhibitory junction potentials in all GSM consist of at least two kinetically differing components: one of them (fast) is very specifically blocked by apamin, while another (more slow) is specifically blocked by charibdotoxin, a polypeptide from scorpion venom. Now it is generally recognized that the mechanisms of both these toxin actions are related to the blocking of Ca2+-activated K + channels (Kca) of the smooth muscle cell (SMC) plasma membrane: charibdotoxin is a specific blocker of high-conductance Kca, and apamin is a specific blocker of small (low-)-conductance Kc~ (SKc,).…”