Tachykinin NK1 and NK2 receptors mediate inhibitory vs excitatory motor responses in human isolated corpus cavernosum and spongiosum.

Motor effects produced by tachykinins were studied in human isolated corpus spongiosum and cavernosum. In quiescent preparations neurokinin A caused potent contractions (pD(2)=8.3 - 7.9 respectively) prevented by the NK(2) receptor-selective antagonist nepadutant, whereas [Sar(9)]SP sulfone and senktide (NK(1) and NK(3) receptor-selective agonists) produced no effect or spare contractions. In KCl-precontracted corpus spongiosum septide (pD(2)=7.1) and [Sar(9)]SP sulfone (pD(2)=7.7) produced tetrodotoxin-resistant relaxations, abolished by the tachykinin NK(1) receptor-selective antagonist SR 140333. [Sar(9)]SP sulfone (1 microM) produced similar relaxations in precontracted corpus cavernosum. Electrical field stimulation (EFS) elicited tetrodotoxin-sensitive relaxations, which were additive to those produced by [Sar(9)]SP sulfone. N(omega)-nitro-L-arginine (L-NOARG) totally prevented both [Sar(9)]SP sulfone- and EFS-induced relaxations. These results show that tachykinin NK(1) and NK(2) receptors mediate opposite motor effects in human penile tissues, suggesting a possible modulatory role of tachykinins on smooth muscle tone in these organs.