PREJUNCTIONAL MODULATION OF NORADRENALINE RELEASE IN MOUSE AND RAT VAS-DEFERENS - CONTRIBUTION OF P(1)-PURINOCEPTORS AND P(2)-PURINOCEPTORS

1 Prejunctional purinoceptors modulating the release of noradrenaline were compared in mouse and rat vas deferens. Tissue slices were preincubated with [H-3]-noradrenaline and then superfused and stimulated electrically, in most experiments by trains of 60 pulses, 1 Hz. 2 In mouse vas deferens, 2-chloroadenosine (IC50 0.24 mum), beta,gamma-methylene-ATP (IC50 3.8 muM), alpha,beta-methylene-ATP (IC50 2.9 muM) and 2-methylthio-ATP (only 30 muM tested) reduced the evoked overflow of tritium. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), 10 nM, antagonized the effect of 2-chloroadenosine (apparent pK(B) 10.2) as well as of beta,gamma-methylene-ATP (apparent pK(B) 9.6) and alpha,beta-methylene-ATP. Suramin, 300 muM, attenuated the effect of 2-chloroadenosine at best very slightly, antagonized the effect of beta,gamma-methylene-ATP (apparent pK(B) 4.5) and, when combined with DPCPX 10 nm, caused a further marked shift to the right of the concentration-response curve of beta,gamma-methylene-ATP beyond the shift produced by DPCPX alone. 3 In rat vas deferens, 2-chloroadenosine (IC50 0.20 muM), beta,gamma-methylene-ATP (IC50 4.8 muM), alpha,beta-methylene-ATP (IC50 3.0 muM) and 2-methylthio-ATP (only 30 muM tested) also reduced the evoked overflow of tritium. DPCPX, 10 nm, antagonized the effect of 2-chloroadenosine (apparent pK(B) 9.7) as well as of beta,gamma-methylene-ATP (apparent pK(B) 9.6) and alpha,beta-methylene-ATP. Suramin, 300 muM, did not change the effect of 2-chloroadenosine, attenuated the effect of beta,gamma-methylene-ATP at best very slightly and, when combined with DPCPX, caused at best a very small shift to the right of the concentration-response curve of beta,gamma-methylene-ATP beyond the shift produced by DPCPX alone. 4 It is concluded that prejunctional purinoceptor mechanisms in mouse and rat vas deferens are similar. In either species, both nucleosides such as adenosine and nucleotides such as beta,gamma-methylene-ATP activate a common release-inhibiting receptor which is a P1- or, more specifically, A1-purinoceptor. There seems to be no need to postulate the existence of a novel prejunctional P3-purinoceptor. Moreover, the sympathetic terminal axons possess an additional P2-purinoceptor in both species which is activated by some nucleotides such as beta,gamma-methylene-ATP and 2-methylthio-ATP, although the activation of the P2-purinoceptor by beta,gamma-methylene-ATP is difficult to demonstrate in the rat.