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.
Patacchini
Riccardo
R
Department of Pharmacology, Menarini Ricerche S.p.A., Via Rismondo 12/A, 50131 Florence, Italy. chimfarm@menarini-richerche.it
Barbagli
Guido
G
Palminteri
Enzo
E
Lazzeri
Massimo
M
Turini
Damiano
D
Maggi
Carlo Alberto
CA
D000328:Adult; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D010413:Penis / Q000187:drug effects / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015320:Tachykinins / Q000502:physiology; D014521:Urethra / Q000187:drug effects / Q000502:physiology
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins