Phospholipase C activation by endothelin-1 and noradrenaline in isolated penile erectile tissue from rabbit.
The effects of endothelin-1 and noradrenaline on phospholipase C activity in the rabbit isolated corpus cavernosum were investigated by measuring the accumulation of inositol phosphates. Both endothelin-1 and noradrenaline caused a time- and concentration-dependent increase in the accumulation of 3H-inositol phosphates in preparations prelabelled with 3H-myo-inositol. The reaction was slow in onset with no significant accumulation of 3H-inositol phosphates, including inositol trisphosphate, demonstrable during the first 15 minutes. At 60 minutes, the mean increases in 3H-inositol inositol phosphates induced by 3 x 10(-7) M endothelin-1 and 10(-3) M noradrenaline amounted to 341 and 530% of time-matched controls, respectively. However, when given at concentrations having the same contractile amplitude on rabbit corpus cavernosum, there was no difference in the amounts of 3H-inositol phosphates generated by endothelin-1 and noradrenaline. Prazosin (10(-6) M) significantly inhibited the stimulatory effect of noradrenaline on phosphoinositide hydrolysis. Pretreatment with 10(-6) M nimodipine did not reduce the increases in 3H-inositol phosphates induced by 3 x 10(-7) M endothelin-1 and 10(-3)M noradrenaline. Also in Ca(2+)-free medium, both agonists had significant stimulatory effects on phosphoinositide turnover, although under this condition, the responses were greatly reduced. The results suggest that exogenous endothelin-1 and noradrenaline activate phospholipase C in corpus cavernosum, and that this mechanism is partly independent of extracellular Ca2+. Considering the slow onset of action, phospholipase C activation is probably not directly involved in rapid contractile events, but may be of importance in the long-term regulation of penile smooth muscle tone.
Holmquist
F
F
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Persson
K
K
Garcia-Pascual
A
A
Andersson
K E
KE
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010410:Penile Erection / Q000502:physiology*; D011817:Rabbits; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism*
D016232:Endothelins; D010738:Type C Phospholipases; D009638:Norepinephrine