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

Ryosuke Takahashi, Junji Nishimura, Katsuya Hirano, Seiji Naito, Hideo Kanaide

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Pages (from-to)845-854
Number of pages10
JournalBritish Journal of Pharmacology
Volume137
Issue number6
DOIs
Publication statusPublished - Nov 1 2002

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Tachykinins
Rabbits
Neurokinin B
Neurokinin A
Neurokinin-1 Receptors
Substance P
Neurokinin-3 Receptors
Neurokinin-2 Receptors
Fluorometry
Endopeptidases
Myofibrils
NG-Nitroarginine Methyl Ester
Protease Inhibitors
Smooth Muscle
Arginine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

The mechanisms for tachykinin-induced contractions of the rabbit corpus cavernosum. / Takahashi, Ryosuke; Nishimura, Junji; Hirano, Katsuya; Naito, Seiji; Kanaide, Hideo.

In: British Journal of Pharmacology, Vol. 137, No. 6, 01.11.2002, p. 845-854.

Research output: Contribution to journalArticle

Takahashi, R, Nishimura, J, Hirano, K, Naito, S & Kanaide, H 2002, 'The mechanisms for tachykinin-induced contractions of the rabbit corpus cavernosum', British Journal of Pharmacology, vol. 137, no. 6, pp. 845-854. https://doi.org/10.1038/sj.bjp.0704938
Takahashi, Ryosuke ; Nishimura, Junji ; Hirano, Katsuya ; Naito, Seiji ; Kanaide, Hideo. / The mechanisms for tachykinin-induced contractions of the rabbit corpus cavernosum. In: British Journal of Pharmacology. 2002 ; Vol. 137, No. 6. pp. 845-854.
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AB - 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.

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