SURAMIN AS AN INHIBITOR OF SYMPATHETIC EXCITATORY. JUNCTION POTENTIALS: STUDY IN GUINEA PIG ISOLATED VAS DEFERENS

Abstract

Introduction. Suramin, as a selective P2x-Pourinoceptor antagonist can inhibit the sympathetic excitatory junction potentials (SEJPs). Experiments have shown that the biphasic contractile responses (bcr) in smooth muscles of vascular and vas deferens (vds) is evoked by cotransmission of ATP and neuradrenaline. Therefore, vds is considered as a model for studying the role of A TP and antagonizing its effect. By using different concentrations of Suramin, its antagonistic effect in phase one of bcr is observed To confirm the purinergic origin of SEJPs, some experiments should be performed electrophysiologically at different concentrations of Suramin.
Methods. Suramin was dissolved in distilled water and after diluting with physiological salt solution freezed as a stock solution at concentration of 10^-1M. After killing and dissecting the albino male guinea pigs (weighing 2S0-300 gm), both testes were pushed up to give out the whole vds. The vds was cleaned from surrounding tissues and cut from epididymic and prostatic ends. vds was maintained at 3SC in physiological salt solution bubbled with 9S percent O₂ and 5 percent CO₂. Intracellular microelectrodes (with resistance of 20-40 MQ) recordings were made from prostatic end of vds.
Results. The resting membrane potential of the control smooth muscle cells was 67.4±.0.7 mV (n=48). Electrical stimulation at frequency of 0.5 Hz evokes SEJPs which are magnified consistently due to facilitation. Mean magnitude of fully facilitated SEJPs which were evoked from control cells was 8.5±0.8 mV (n=23). Further facilitation was evoked at frequencies of 1 Hz or 2 Hz, because SEJPs were obtained at the threshold limit to begin the action potentials which were 55 mV in most cells. It was difficult to estimate correctly the threshold potential in a cell because disseminated potential might conduct to the other cell and the penetration of microelectrode into cell was impossible due to contraction of smooth muscle cell. All control experiments were performed by using stimulation at frequency of 0.5 Hz and the effects of drug in fully facilitated SEJPS were tested. Suramin produced the dose dependent reduction in SEJPs.
Discussion. SEJPs are inhibited by Suramin in guinea pig vds. The mean magnitude of SEJPs is not reduced even at frequencies until 8 Hz by using selective a₁-adrenoceptor antagonists (prazosin). The addition of Suramin does not change the resting membrane potential of smooth muscle cells during exposures of over one hour and further reduction in SEJPs. Suramin can block the SEJPs in vds and the role of A TP to evoke the bcr is indicated by it.