EP 91073 prevents EP 80661-induced penile erection: new evidence for the existence of specific EP peptide receptors mediating penile erection

The effect of EP 91073, EP 51389, EP 70555 and EP 51216, peptide analogues of the growth hormone releasing peptide hexarelin, on penile erection induc ed by EP 80661 or EP 60761 injected into the paraventricular nucleus of the hypothalamus, was studied in male rats. Of the above peptides only EP 9107 3 (0.2-1 mug) was found capable of reducing penile erection induced by EP 8 0661 or EP 60761, when given into the paraventricular nucleus. Despite its ability to prevent EP peptide-induced penile erection, EP 91073 (1 mug) was unable to prevent penile erection induced by the dopamine receptor agonist apomorphine (50 ng), oxytocin (30 ng) and N-methyl-D-aspartic acid (50 ng) , when given into the paraventricular nucleus 10 min prior to the above sub stances. The EP 91073-induced prevention of penile erection occurred with a reduction in the increase in nitric oxide production that occurs in the pa raventricular nucleus concomitant to penile erection induced by EP 80661 an d EP 60761, as measured by intracerebral vertical microdialysis. The presen t results are in line with the hypothesis that EP 80661 and EP 60761 induce penile erection by activating specific receptors in the paraventricular nu cleus, located possibly in oxytocinergic neurons mediating penile erection, and show that EP 91073 acts as an antagonist of these EP peptide receptors mediating penile erection. (C) 2001 Elsevier Science Ltd. All rights reser ved.