Holmquist F, Persson K, Garcia-Pascual A, Andersson K E
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
J Urol. 1992 Jun;147(6):1632-5. doi: 10.1016/s0022-5347(17)37667-x.
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.
