P1-purinoceptor-mediated modulation of neural noradrenaline and ATP release in guinea-pig vas deferens.
The effect of P1-purinoceptor activation on contractions, release of noradrenaline and release of ATP elicited by electrical field stimulation (210 pulses, 7 Hz) was studied in the superfused vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of total tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. Electrical stimulation elicited reproducible contraction, tritium overflow and ATP overflow. In the absence of other drugs, adenosine (10-100 microM) did not change evoked contractions but reduced the evoked overflow of tritium and ATP. In subsequent experiments alpha 1-adrenoceptors were blocked by prazosin, P2-purinoceptors by suramin and alpha 2-adrenoceptors by rauwolscine. No or almost no contraction remained under these conditions. The evoked overflow of tritium was 505% and the evoked overflow of ATP 34% of that observed in the absence of prazosin, suramin and rauwolscine. Adenosine (1-100 microM) again reduced the evoked overflow of tritium and ATP, and so did the A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 0.032-0.32 microM). Adenosine and CCPA decreased the evoked overflow of ATP to a greater extent than the evoked overflow of tritium. It is concluded that neural release of both postganglionic sympathetic cotransmitters, noradrenaline and ATP, is decreased upon activation of prejunctional P1- (A1-) purinoceptors in guinea-pig vas deferens. The A1-receptor-mediated inhibition of the release of ATP is more marked than the inhibition of the release of noradrenaline, a pattern opposite to the inhibition produced by activation of prejunctional alpha 2-autoreceptors.
Driessen
B
B
Pharmakologisches Institut, Universität Freiburg, Germany.
von Kügelgen
I
I
Starke
K
K
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D015016:Yohimbine; C058394:2-chloro-N(6)cyclopentyladenosine; D013498:Suramin; D000255:Adenosine Triphosphate; D000241:Adenosine; D009638:Norepinephrine; D011224:Prazosin