Role of adenosine and P2 receptors in the penile tumescence in anesthetized dogs

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Abstract

We studied the role of adenosine and P2 receptors in the pelvic nerve stimulation-induced penile tumescence in anesthetized dogs. A local intracavernous injection of adenosine induced the tumescence, which was abolished by intracavernous 8-(p-sulfophenyl)theophylline (8-SPT), an unspecific adenosine receptor antagonist, and by 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol (ZM241385), an adenosine A2A receptor antagonist. ATP also induced the tumescence, which was diminished by 8-SPT, but not by reactive blue-2, a P2 receptor antagonist. Neither intracavernous β, γ-meATP nor ADPβS, P2X and P2Y receptor agonists, induced tumescence. NG-nitro-l-arginine (l-NAME), a nitric oxide synthase inhibitor, and T-1032, a phosphodiesterase type V inhibitor, had no effects on the tumescence induced by adenosine. 8-SPT and reactive blue-2 had no effects on the tumescence induced by pelvic nerve stimulation. These results show that although exogenous adenosine and ATP induce tumescence, neither the adenosine nor the P2 receptor is involved in the tumescence induced by pelvic nerve stimulation in anesthetized dogs.

Introduction

Many studies have shown that nitric oxide (NO) synthesized from l-arginine mainly mediates the relaxation of penile corpus cavernosum muscle and the intracavernous pressor response to nerve stimulation in a variety of mammals Anderson, 1993, Ignarro et al., 1990, Trigo-Rocha et al., 1993. Although it has also been reported that several other endogenous neurotransmitters such as adenosine, ATP, vasoactive intestinal polypeptide and calcitonin gene-related peptide exist in the corpus cavernosum, their roles in erection are still unclear (Andersson and Wagner, 1995). Adenosine and ATP are reported to induce tumescence when they are injected into the corpus cavernosa in dogs and to relax the isolated corpus smooth muscles from humans, rats and rabbits Chiang et al., 1994, Filippi et al., 1999, Gur and Ozturk, 2000, Ragazzi et al., 1996, Takahashi et al., 1992a, Takahashi et al., 1992b, Wu et al., 1993. In addition, the nerve stimulation-induced relaxation of the isolated corpus smooth muscle is inhibited by 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2 receptor antagonist (Chiang et al., 1994). These data suggest that adenosine and ATP may contribute to physiological penile erection, but there are no reports about their roles in erection in in vivo models.

We now studied the roles of adenosine and ATP in pelvic nerve-stimulated tumescence in anesthetized dogs using some receptor antagonists.

Section snippets

Materials and methods

This project was approved by the Ethical Committee at Tanabe Seiyaku and all efforts were made to minimize animal suffering and to reduce the number of animals used.

Results

Intracavernous adenosine injection (0.1, 0.3, and 1 mM, 0.5 ml/injection) induced tumescence dose-dependently (Fig. 1A). This tumescence could be induced repeatedly to the same degree at least three times (1 mM, 0.5 ml/injection, i.c.) (Fig. 1B) and was abolished by pretreatment with 8-SPT (1 mM, 0.5 ml/injection, i.c.), an unspecific adenosine receptor antagonist, and with ZM241385 (1 mM, 0.5 ml/injection, i.c.), a specific adenosine A2A receptor antagonist (Fig. 2A,B). l-NAME (30 mM, 0.5

Discussion

Extensive reduction by l-NAME and potentiation by the phosphodiesterase type V inhibitor have suggested an essential role of NO in the pelvic nerve-stimulated tumescence in anesthetized dogs Noto et al., 2000, Trigo-Rocha et al., 1993. Although intracavernous injections of adenosine and ATP were reported to induce tumescence in dogs Takahashi et al., 1992a, Takahashi et al., 1992b, their roles in the tumescence induced by pelvic nerve stimulation were not clear (Andersson and Wagner, 1995). The

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