ATP and endogenous agonists inhibit evoked [3H]-noradrenaline release in rat iris via A1 and P2y-like purinoceptors.
Effects of ATP, adenosine and purinoceptor antagonists on field stimulation-evoked (3 Hz, 2 min) [3H]-noradrenaline overflow were investigated in the rat isolated iris. ATP and adenosine inhibited the evoked overflow of [3H]-noradrenaline. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) shifted the concentration-response curve of ATP to the right in a concentration-dependent manner, but with a potency (-log KB = 7.88) much lower than expected for an A1 adenosine receptor. In the continuous presence of DPCPX, the ATP-induced prejunctional inhibition was unaffected by suramin (100 mumol/l) and DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, 50 mumol/l) but was antagonized by the P2Y-receptor antagonist cibacron blue (= reactive blue 2; 30 and 100 mumol/l, -log KB = 4.7) and alpha,beta-methylene-ATP (10 mumol/l). Whereas the evoked [3H]-noradrenaline overflow was unaffected by suramin and DIDS, cibacron blue and alpha,beta-methylene-ATP caused a small and transient increase. Cibacron blue at 30 mumol/l failed to antagonize the inhibition of evoked [3H]-noradrenaline overflow that adenosine produced in the absence of DPCPX. Basal [3H]-noradrenaline overflow was enhanced by cibacron blue, not changed by alpha,beta-methylene-ATP and DIDS, and decreased by suramin. The results show that exogenous ATP inhibits sympathetic neurotransmission in the rat iris via A1 and P2Y-like purinoceptors. The latter have a low apparent affinity for cibacron blue and probably are blocked by alpha,beta-methylene-ATP. Under the present conditions, endogenous purines exert a tonic inhibition not only via A1- but also via these P2Y-receptors.
Fuder
H
H
Pharmakologisches Institut, Universität Mainz, Germany.
Muth
U
U
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007498:Iris / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D013498:Suramin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014227:Triazines; D014970:Xanthines; C012842:Cibacron Blue F 3GA; D013498:Suramin; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D009638:Norepinephrine