Prejunctional modulation of noradrenaline release in mouse and rat vas deferens: contribution of P1- and P2-purinoceptors.
1. Prejunctional purinoceptors modulating the release of noradrenaline were compared in mouse and rat vas deferens. Tissue slices were preincubated with [3H]-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 microM), beta,gamma-methylene-ATP (IC50 3.8 microM), alpha,beta-methylene-ATP (IC50 2.9 microM) and 2-methylthio-ATP (only 30 microM tested) reduced the evoked overflow of tritium. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), 10 nM, antagonized the effect of 2-chloro-adenosine (apparent pKB 10.2) as well as of beta,gamma-methylene-ATP (apparent pKB 9.6) and alpha,beta-methylene-ATP. Suramin, 300 microM, attenuated the effect of 2-chloroadenosine at best very slightly, antagonized the effect of beta,gamma-methylene-ATP (apparent pKB 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 microM), beta,gamma-methylene-ATP (IC50 4.8 microM), alpha,beta-methylene-ATP (IC50 3.0 microM) and 2-methylthio-ATP (only 30 microM tested) also reduced the evoked overflow of tritium. DPCPX, 10 nM, antagonized the effect of 2-chloroadenosine (apparent pKB 9.7) as well as of beta,gamma-methylene-ATP (apparent pKB 9.6) and alpha,beta-methylene-ATP. Suramin, 300 microM, 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 Pl- 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.
Kurz
K
K
Pharmakologisches Institut, Freiburg, Germany.
von Kügelgen
I
I
Starke
K
K
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014970:Xanthines; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D013498:Suramin; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine