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

1. 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. 2. Tachykinins induced contractions in the rabbit corpus cavernosum in a concentration-dependent manner. The potency order was SP > NKA > NKB. 3. The tachykinin-induced contractions were enhanced by phosphoramidon (PPAD), an endopeptidase inhibitor, but not by Nω-nitro-L-arginine methylester (L-NAME). 4. 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. 5. 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. 6. In α-toxin permeabilized preparations, tachykinins induced an additional force development at a constant [Ca ²⁺] _i. 7. 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.