The mechanisms for tachykinin‐induced contractions of the rabbit corpus cavernosum

This study was designed to investigate the mechanisms for the contractions induced by tachykinins (substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)) in the rabbit corpus cavernosum strips, using fura‐PE3 fluorimetry and α‐toxin permeabilization. Tachykinins induced contractions in the rabbit corpus cavernosum in a concentration‐dependent manner. The potency order was SP>NKA>NKB. The tachykinin‐induced contractions were enhanced by phosphoramidon (PPAD), an endopeptidase inhibitor, but not by N ω ‐nitro‐ L ‐arginine methylester ( L ‐NAME). The NK 1 receptor selective antagonist, SR 140333 significantly inhibited the tachykinin‐induced contractions. Although the NK 2 receptor selective antagonist, SR 48968 alone did not influence the effects of tachykinins, it potentiated the inhibitory effect of SR 140333. The NK 3 receptor selective antagonist, SR142801 had no effect. In the rabbit corpus cavernosum, tachykinins induced sustained increases in [Ca 2+ ] i and tension in normal PSS, while only small transient increases in [Ca 2+ ] i and tension were observed in Ca 2+ ‐free solution. In α‐toxin permeabilized preparations, tachykinins induced an additional force development at a constant [Ca 2+ ] i . These results indicated that in the rabbit corpus cavernosum: (1) Tachykinins induced contractions by increasing both the [Ca 2+ ] i and myofilament Ca 2+ sensitivity; (2) The tachykinin‐induced [Ca 2+ ] i elevations were mainly due to the Ca 2+ influx; (3) Tachykinin‐induced contractions were mainly mediated through the activation of NK 1 receptor expressed in the rabbit corpus cavernosum smooth muscle, and affected by the endopeptidase activity and (4) Tachykinins may thus play a role in controlling the corpus cavernosum tone.British Journal of Pharmacology (2002) 137 , 845–854. doi: 10.1038/sj.bjp.0704938