As with em /em 1-adrenoceptors, P2X1-receptors appear to mediate excitatory effects, and both noradrenaline and ATP are released from sympathetic nerve terminals within the prostate gland in response to electrical-field stimulation

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As with em /em 1-adrenoceptors, P2X1-receptors appear to mediate excitatory effects, and both noradrenaline and ATP are released from sympathetic nerve terminals within the prostate gland in response to electrical-field stimulation. P2X1-receptors are the principle P2-receptors in smooth muscle from genitourinary tissues such as the rat vas deferens (Khakh em et al /em ., 1995), rat and guinea-pig bladder (Inoue & Brading, 1990; Bo & Burnstock, 1992) as well as from rat vascular smooth muscle (Bo Coenzyme Q10 (CoQ10) & Burnstock, 1993; Evans & Kennedy, 1994). St. Rabbit Polyclonal to CDK1/CDC2 (phospho-Thr14) Louis, U.S.A.), AMP (Sigma, St. Louis, U.S.A.), ATP (Sigma, St. Louis, U.S.A.), guanethidine (Sigma, St. Louis, U.S.A.), TukeyCKramer correction). Prazosin (0.3 TukeyCKramer correction). #Indicates a significant difference from response in the presence of prazosin (#TukeyCKramer correction). Suramin (100 in the presence and absence of suramin (100 em /em M))C1). em n /em =6 animals for each agonist. Discussion The results of this study indicate that P2X1-receptors as well as em /em 1-adrenoceptors are present on the smooth muscle of the rat prostate. As with em /em 1-adrenoceptors, P2X1-receptors appear to mediate excitatory effects, and both noradrenaline and ATP are released from sympathetic nerve terminals within the prostate gland in response to electrical-field stimulation. P2X1-receptors are the principle P2-receptors in smooth muscle from genitourinary tissues such as the rat vas deferens (Khakh em et al /em ., 1995), rat and guinea-pig bladder (Inoue & Brading, 1990; Bo & Burnstock, 1992) as well as from rat vascular smooth muscle (Bo & Burnstock, 1993; Evans & Kennedy, 1994). The function of P2X1-receptors in these tissues is to mediate smooth muscle contraction. ATP is released from the nerve fibres innervating these tissues to act on these receptors. In the present study, we have also demonstrated the release of ATP in response to electrical-field stimulation, which is able to elicit contraction of the rat prostate gland. The possible significance of the role of ATP in prostatic function has been emphasized with reports of expression of P2-receptors (Fang em et al /em ., 1992; Janssens em et al /em ., 1996; Longhurst em et al /em ., 1996; Wasilenko em et al /em ., 1997) and of ecto 5-nucleotidase (Konrad em et al /em ., 1998) in human prostate. Previous studies, which have demonstrated P2X-receptors for ATP in the rat prostate (Lee em et al /em ., 2000; Slater em et al /em ., 2000), have produced conflicting results regarding the subtype of these P2-receptors. The immunohistochemical studies conducted in our study are in agreement with Lee em et al /em . (2000) who also showed a predominance of the P2X1-receptor subtype in the fibromuscular stroma of the rat prostate. Slater em et al /em . (2000) reported a predominance of the P2X2-receptor subtype in the stroma of the rat prostate, but we found no evidence of the presence of this P2-receptor subtype in the rat prostatic fibromuscular stroma in our study. Our immunohistochemical demonstration of the presence of a P2X1-receptor subtype in the fibromuscular stroma of the rat prostate was supported further by its apparent colocalization with actin and our functional contractility studies. Studies of the excitatory effects of the naturally occurring purines showed that ATP was able to elicit contractions of the rat prostate, while AMP and adenosine were inactive. This is consistent with actions at P2-receptors for ATP rather than adenosine receptors (Burnstock, 1978). The sensitivity of these contractile responses to suramin further implicates P2-receptors. The relative order of potency of ATP and its methyl phosphate isosteres in causing contraction of the tissue, namely, em /em methylene ATP em /em methylene ATP ATP is consistent with the original subclassification of the P2-receptors mediating these effects as the P2X-receptor subtype (Burnstock & Kennedy, 1985). The sensitivity and rapid desensitization to em /em methylene ATP in combination with suramin sensitivity is indicative of either a P2X1- or P2X3-receptor subtype (Humphrey em et al /em ., 1998). The greater potency of em /em methylene ATP when compared to ATP suggests that contractions are caused by the stimulation of P2X1-receptors (Humphrey em et al /em ., 1998). In addition, our calculated mean apparent em K /em B values (2.5C5.4 em /em M) for suramin compare favourably with previously reported IC50 values (1C5 Coenzyme Q10 (CoQ10) em /em M) at P2X1-receptors (Humphrey em et al /em ., 1998). Indeed, the relative potencies of these compounds on the prostate gland are similar to those observed previously by us in the rat cauda Coenzyme Q10 (CoQ10) epididymis (Ventura & Pennefather, 1991). In that study, we found em /em methylene ATP to be 1150 times more potent than ATP. em /em Methylene ATP was approximately 17 times more potent than ATP. The differences in the magnitude of the potency ratios in the present study.