Isolated Rabbit Corpus Cavernosum Research Articles

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 phosphates induced by 3 × 10−7M endothelin-1 and 10−3M 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 (10−6M) significantly inhibited the stimulatory effect of noradrenaline on phosphoinositide hydrolysis. Pretreatment with 10−6M nimodipine did not reduce the increases in 3H-inositol phosphates induced by 3 × 10−7M endothelin-1 and 10−3M noradrenaline. Also in Ca2+-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.

ウサギ陰茎海綿体に対する各種 vasoactive drug の作用に関する検討

Recently, intracavernous injection of some vasoactive drugs has been performed for the diagnosis and treatment of impotence. Despite extensive studies the mechanism of erection is still obscure. Therefore, the author studied the effects of some vasoactive drugs on isolated rabbit corpus cavernosum penis. Norepinephrine, phenylephrine or clonidine caused contraction of isolated rabbit corpus cavernosum strips in a concentration-dependent manner. This contractile effect was more potent with norepinephrine and phenylephrine than with clonidine. Prazosin was more effective than yohimbine in inhibiting norepinephrine-induced contractions. Papaverine and verapamil strongly relaxed the strips contracted by norepinephrine. Prostaglandin E1 also showed a relaxant effect. Low concentrations of isoproterenol caused relaxation, but in high concentrations it caused contraction. Acetylcholine relaxed norepinephrine-contracted strips in a concentration-dependent manner. Although the relaxant effect of acetylcholine was weaker than that of papaverine at high concentrations, acetylcholine and papaverine were almost equally effective at low concentrations. Vasoactive intestinal polypeptide relaxed the strips, and it was significantly more potent than papaverine. These findings suggest that both postsynaptic alpha 1-adrenoceptors and alpha 2-adrenoceptors are present in rabbit corpus cavernosum penis, and that alpha 1-adrenoceptors are predominant. The flaccid state of the rabbit penis seems to be maintained mainly by alpha 1-adrenoceptors. Verapamil seems to be useful for the diagnosis and treatment of impotence as papaverine. Acetylcholine and vasoactive intestinal polypeptide may be neurotransmitters involved in erection.