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PMID: 8306088 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Prejunctional modulation of noradrenaline release in mouse and rat vas deferens: contribution of P1- and P2-purinoceptors.

British journal of pharmacology ·Vol. 110 ·No. 4 ·1993-12-00 ·Pages 1465-72

Kurz K, von Kügelgen I, Starke K

Abstract

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.

MeSH Terms
Adenosine Triphosphate/analogs & derivatives,pharmacology Animals In Vitro Techniques Male Mice Norepinephrine/metabolism Rats Rats, Wistar Receptors, Purinergic P1/physiology Receptors, Purinergic P2/physiology Suramin/pharmacology Vas Deferens/drug effects,metabolism Xanthines/pharmacology
Chemicals
Receptors, Purinergic P1 Receptors, Purinergic P2 Xanthines 5'-adenylyl (beta,gamma-methylene)diphosphonate Suramin Adenosine Triphosphate 1,3-dipropyl-8-cyclopentylxanthine alpha,beta-methyleneadenosine 5'-triphosphate Norepinephrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kurz K
Pharmakologisches Institut, Freiburg, Germany.
von Kügelgen I
Starke K
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1993.tb13986.x
Published
1993-12-00
Pages
1465-72
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2175891
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1476-5381.1993.tb13986.x PMC Full Text View journal details
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