Selective enhancement by an adenosine A1 receptor agonist of agents inducing contraction of the rat vas deferens.

The adenosine analogue N6-cyclopentyladenosine (CPA), acting via postjunctional A1 receptors, has been shown to enhance contractions of the rat vas deferens induced by adenosine 5'-triphosphate (ATP), the sympathetic cotransmitter in this tissue. The aim of the present study was to examine the ability of CPA to enhance contractions induced by other contractile agents. CPA (0.01-0.3 microM) enhanced contractions induced by exogenous ATP (10 microM), 5-hydroxytryptamine (5-HT) (3 microM), tyramine (10 microM), 2-methyl-5-hydroxytryptamine (2-Me-5-HT) (10 microM) and KCl (35 mM) and this enhancement was blocked by an A1-selective concentration (3 nM) of 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX). CPA failed to enhance contractions induced by exogenous noradrenaline (NA) (1 microM or 10 microM), bradykinin (0.1 microM), phenylephrine (3 microM) or carbachol (10 microM). The contractions induced by ATP (10 microM), 5-HT (3 microM), 2-Me-5-HT (10 microM) and KCl (35 mM) were unaffected by tetrodotoxin (1 microM) as well as by desensitisation of the P2x-purinoceptors with the ATP analogue adenosine 5'-(alpha, beta-methylene) triphosphonate. The contractions induced by tyramine (10 microM) and 2-Me-5-HT (10 microM) were blocked by prazosin (100 nM) or by imipramine (1 microM). Ketanserin (10 nM) antagonised the response to 5-HT giving a dose-ratio of 12.9 corresponding to an apparent pA2 of 9.1. In conclusion, the A1-mediated effect was clearly selective for certain contractile agents and not due to a non-specific increase in contractility of the tissue. CPA enhanced contractions induced by both ATP and indirect sympathomimetics which release endogenous NA, and this enhancement of the two sympathetic cotransmitters may have a functional significance, and demonstrates the complexity of the neuromodulatory effects of adenosine in the rat vas deferens.