title: The mechanisms for tachykinin-induced contractions of the rabbit corpus cavernosum.
abstract: 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 alpha-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 N(omega)-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 alpha-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.
authors.affiliation: Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Junji
authors.initials: J
authors.lastname: Nishimura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirano
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Hideo
authors.initials: H
authors.lastname: Kanaide
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010413:Penis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D011817:Rabbits; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000494:pharmacology
chemical_list: D001549:Benzamides; D006020:Glycopeptides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C085215:SR 140333; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; D015287:Neurokinin B; D010738:Type C Phospholipases; C091554:SR 142801; D002118:Calcium; C008890:phosphoramidon; D019331:NG-Nitroarginine Methyl Ester