[CA(2+)](I)-SENSITIVE, IP(3)-INDEPENDENT CA(2+) INFLUX IN SMOOTH-MUSCLE OF RAT VAS-DEFERENS REVEALED BY PROCAINE

1 The actions of procaine (10 mM) on noradrenaline-induced effects on Ca-45-influx, Ca-45-efflux, Ca-45-content, total inositol phosphates, inositol-1,4,5-trisphosphate, and contractile status of the rat vas deferens were examined. 2 Noradrenaline alone had no effect on Ca-45-influx or Ca-45-content, but released Ca2+ from intracellular stores as indicated by an increased Ca-45-efflux and increased total inositol phosphates, specifically inositol-1,4,5-trisphosphate, leading to contraction of the rat vas deferens. 3 Noradrenaline, in the presence of 10 mm procaine, increased Ca-45-influx and Ca-45-content. Procaine blocked the noradrenaline-induced Ca-45-efflux, the increase in total inositol phosphates, the increase in inositol-1,4,5-trisphosphate, and contraction. 4 The noradrenaline-induced increase in Ca-45 influx which was observed in the presence of procaine was abolished by phentolamine and nifedipine but was not altered significantly by propranolol suggesting that, in the presence of procaine, noradrenaline activates dihydropyridine-sensitive calcium channels through alpha-adrenoceptors. 5 These findings indicate that, in the rat vas deferens, noradrenaline induces contraction by releasing intracellularly stored Ca2+. The effects of procaine appear to be due to its ability to block the release of Ca2+ from intracellular stores. Furthermore, the simultaneous increase in Ca-45 influx and inhibition of inositol-1,4,5-trisphosphate formation in tissues treated with procaine plus noradrenaline indicates that Ca2+ influx is independent of inositol-1,4,5-trisphosphate formation.