Effects of alpha,beta-methylene ATP on the prejunctional purinoceptors of the sympathetic nerves of the rat caudal artery.
The effects of alpha,beta-methylene ATP, an agent known to stimulate and then to desensitize P2-purinoceptors, on the release of endogenous norepinephrine from the electrically stimulated rat caudal artery were determined. Norepinephrine was quantified by high-performance liquid chromatography-electrochemical detection techniques. alpha,beta-Methylene ATP over the concentration range of 1 to 100 microM did not affect the release of norepinephrine evoked by stimulation for 3 min at 1 Hz. In contrast, 2-chloroadenosine, a P1 receptor agonist, and beta,gamma-methylene ATP, a P2 receptor agonist, produced a concentration-related inhibition of the release of norepinephrine presumably by activating prejunctional purinoceptors. The failure of alpha,beta-methylene ATP to inhibit transmitter release was apparently not related to the length of pretreatment with this agent because pretreatments of 0.5 to 15 min yielded similar results. These findings indicate that the ability of alpha,beta-methylene ATP to decrease excitatory junction potentials and vasoconstriction of the caudal artery, as reported by others, is not due to a decrease in the release of transmitter. In spite of not possessing agonistic properties, alpha,beta-methylene ATP does interact with prejunctional purinoceptors as judged by the finding that the inhibitory effects of 2-chloroadenosine and beta,gamma-methylene ATP, but not those of the alpha-2 agonist clonidine, were antagonized by alpha,beta-methylene ATP. alpha,beta-Methylene ATP thus appears to be an antagonist at prejunctional purinoceptors (classified by us previously as P3-purinoceptors). alpha,beta-Methylene ATP also appears to act as an antagonist against endogenously released adenine nucleosides and nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of Nevada School of Medicine, Reno.
K
K
Shinozuka
R A
RA
Bjur
D P
DP
Westfall
D015762:2-Chloroadenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009451:Neuroeffector Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011983:Receptors, Purinergic / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine