[Ca2+]i-sensitive, IP3-independent Ca2+ influx in smooth muscle of rat vas deferens revealed by procaine.
1. The actions of procaine (10 mM) on noradrenaline-induced effects on 45Ca-influx, 45Ca-efflux, 45Ca-content, total inositol phosphates, inositol-1,4,5-trisphosphate, and contractile status of the rat was deferens were examined. 2. Noradrenaline alone had no effect on 45Ca-influx or 45Ca-content, but released Ca2+ from intracellular stores as indicated by an increased 45Ca-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 45Ca-influx and 45Ca-content. Procaine blocked the noradrenaline-induced 45Ca-efflux, the increase in total inositol phosphates, the increase in inositol-1,4,5-trisphosphate, and contraction. 4. The noradrenaline-induced increase in 45Ca 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 45Ca 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.
Khoyi
M A
MA
Department of Pharmacology, University of Nevada School of Medicine, Reno 89557.
Dalziel
H H
HH
Zhang
L
L
Bjur
R A
RA
Gerthoffer
W T
WT
Buxton
I L
IL
Westfall
D P
DP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology*; D051381:Rats; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology*
D013757:Tetraethylammonium Compounds; D011343:Procaine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D009638:Norepinephrine