Effect of the K+ efflux stimulating vasodilator BRL 34915 on 86Rb+ efflux and spontaneous activity in guinea-pig portal vein.
The effect of BRL 34915 on 86Rb+ efflux and myogenic activity was studied simultaneously in guinea-pig portal vein. 86Rb+ was used as a tracer ion for K+. BRL 34915 inhibited myogenic activity with an IC50 value of 12 +/- 2 nM by reducing primarily the frequency of spontaneous contractions. Washout of the substance was followed by hyperreactivity of the vessel. 86Rb+ efflux was slightly reduced by concentrations of BRL 34915 below 100 nM; above 300 nM efflux was increased in a concentration-dependent manner. Above 10 microM BRL 34915, a slow desensitization of the effect on flux was observed during the 10 min application period of the agonist. The Ca2+ entry blocker, isradipine (PN 200-110, 200-500 nM) did not modify BRL 34915-stimulated 86Rb+ efflux at any BRL 34915 concentration tested, indicating that the influx of extracellular Ca2+ through dihydropyridine-sensitive Ca2+ channels is not necessary for this effect. However, by abolishing spontaneous activity, it allowed the 86Rb+ efflux promoting effect of BRL 34915 to be observed at a concentration of 60 nM. The K+ channel blockers tetraethylammonium and 3,4 diaminopyridine inhibited the BRL 34915-induced 86Rb+ efflux with IC50 values of 13 and 3 mM, respectively. Cell permeable derivatives of cyclic AMP and cyclic GMP had no major effect on BRL 34915-induced 86Rb+ flux, indicating that cyclic nucleotide-induced phosphorylation does not play an important modulatory role here. In conclusion, there is an at least 5 fold difference between the concentrations of BRL 34915 necessary to inhibit myogenic activity and those needed to stimulate 86Rb+ efflux. This may be explained by a primary effect of BRL 34915 on the pacemaker cells of the portal vein. explained by a primary effect of BRL 34915 on the pacemaker cells of the portal efflux. This may be
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D019806:Cromakalim; D004347:Drug Interactions; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D011868:Radioisotopes; D012413:Rubidium / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D001578:Benzopyrans; D011758:Pyrroles; D011868:Radioisotopes; D014665:Vasodilator Agents; D019806:Cromakalim; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D012413:Rubidium; D011188:Potassium