Nucleotide modulation of norepinephrine release from sympathetic nerves in the rat vas deferens.
The effects of a number of purinoceptor agonists and antagonists on norepinephrine (NE) overflow were examined in the electrically field-stimulated rat vas deferens. The P1 receptor agonists adenosine and 2-chloroadenosine and the P2 receptor agonists ATP and beta, gamma-methylene ATP all reduced the overflow of NE, which was quantified by high-performance liquid chromatography-electrochemical detection techniques. The P1 receptor antagonist 8-(p-sulfophenyl)-theophylline (8-SPT) and the P2 receptor desensitizing agent alpha, beta-methylene ATP blocked the inhibitory effects of both P1 and P2 receptor agonists. The pyrimidine nucleotide UTP also inhibited NE overflow and this effect was antagonized by 8-SPT. The adenosine uptake inhibitor S-p-nitrobenzyl-6-thioguanosine potentiated and adenosine deaminase blocked the inhibitory effect of adenosine on NE overflow but neither had any effect on the ability of the adenine nucleotides to inhibit NE overflow. These results indicate that adenine nucleotides can act per se, without conversion to adenosine, on a prejunctional receptor to inhibit the release of NE. Because the effects of the adenine nucleotides are antagonized by 8-SPT, it appears that they act at the same receptor as the adenine nucleosides. UTP apparently acts at this receptor as well. These findings suggest that prejunctional purinoceptors on the sympathetic nerves of the rat vas deferens differ from P1 or P2 receptors as usually defined and thus may represent a unique class of receptor (P3) as has been suggested for the prejunctional receptors of the rat caudal artery.
Forsyth
K M
KM
Department of Pharmacology, University of Nevada School of Medicine, Reno.
Bjur
R A
RA
Westfall
D P
DP
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009711:Nucleotides / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011983:Receptors, Purinergic / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism
D018377:Neurotransmitter Agents; D009711:Nucleotides; D011983:Receptors, Purinergic; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine