EFFECT OF THE CA2-CHANNEL AGONIST BAY K-8644 ON THE CONTRACTILE RESPONSES IN HUMAN PLACENTAL VEINS()

1 The aim of the present study was to analyse, in segments of human pl acental veins, the effect of the Ca2+ channel agonist Bay K 8644 (0.1 mu M) and Ca2+ channel antagonists nifedipine (0.1 mu M) and diltiazem (1 mu M) on vascular contractility and Ca-45(2+) uptake. 2 The Ca2+ c hannel agonist Bay K 8644 (0.1 mu M) caused small concentration depend ent contractions that were increased by a moderate membrane depolariza tion with 7.5 mM K+. This increase was reversed by nifedipine and dilt iazem. Ca2+ addition to segments previously depolarized with 75 mM Kand exposed to a Ca2+-free medium caused contractile responses that we re increased by 0.1 mu M Bay K 8644; such an increase was blocked by 0 .1 mu M nifedipine and 1 mu M diltiazem. 3 K+ and 5-HT induced concent ration dependent contractile responses which were increased by Bay K 8 644 (0.1 mu M). Both 0.1 mu M nifedipine and 1 mu M diltiazem inhibite d the increasing effect of Bay K 8644. Bay K 8644 (30 nM and 0.1 mu M) caused an enhancement in Ca-45(2+) accumulation over the basal value, that was increased by membrane depolarization with K+ (7.5, 15 and 30 nM) and inhibited by nifedipine (0.1 mu M). K+ (15 and 30, but not 7. 5 mM) and 5-HT (1 mu M) induced Ca-45(2+) uptake over the basal level that was increased by Bay K 8644 (0.1 mu M). Such an increase was anta gonized by nifedipine (0.1 mu M). 4 These data indicate that: (1) a sm all depolarization with K+ is needed for Bay K 8644 to be able to prod uce consistent contractile responses, suggesting that voltage gated Ca 2+ channels (VGCCs) are not activated in a basal situation in placenta l veins; (2) the increase of 5-HT contraction by Bay K 8644 may be pro duced by either the capability of this amine to depolarize the membran e of smooth muscle cells and subsequent facilitation of Ca2+ influx th rough VGCCs or direct activation by Bay K 8644 of receptor (5-HT) oper ated Ca2+ channels (ROCs), and (3) the increasing effect of Bay K 8644 appears to be due to a Ca2+ entry activation through VGCCs.