Adenosine receptor-induced cyclic AMP generation and inhibition of 5-hydroxytryptamine release in human platelets.
1. We have assessed the effects of adenosine receptor agonists and antagonists on collagen-induced 5-hydroxytryptamine (5-HT) release and cyclic AMP generation in human platelets. 2. 5'-N-ethylcarboxamidoadenosine (NECA) and CGS 21680 elicited accumulations of cyclic AMP with mean EC50 values of 2678 and 980 nM, respectively. The maximal response to CGS 21680 was approximately half that of the response to 10 microM NECA. 3. NECA and CGS 21680 inhibited collagen-induced 5-hydroxytryptamine release with mean EC50 values of 960 and 210 nM, respectively. The maximal response to CGS 21680 was approximately 25% of the response to 10 microM NECA. 4. The A1/A2a-selective adenosine receptor antagonist PD 115,199 was more potent as an inhibitor of NECA-elicited responses than the A1-selective antagonist DPCPX with calculated Ki values of 22-32 nM and > 10 microM, respectively. 5. In the presence of a cyclic AMP phosphodiesterase inhibitor, the effects of CGS 21680 on cyclic AMP accumulation and 5-HT release were enhanced to levels similar to those elicited by 10 microM NECA. In the absence of phosphodiesterase inhibition, CGS 21680 did not antagonise the effects of NECA. Furthermore, endogenous adenosine did not contribute to the effects of CGS 21680 when phosphodiesterase was inhibited. 6. We conclude that an A2a adenosine receptor appears to be involved in the NECA-elicited increases in cyclic AMP levels and inhibition of 5-HT release in human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University Hospital, Nottingham, UK.
J A
JA
Cooper
S J
SJ
Hill
S P
SP
Alexander
P C
PC
Rubin
E H
EH
Horn
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D010627:Phenethylamines / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D011687:Purines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology; D000096926:Benzenesulfonamides
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000241:Adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000959:Antihypertensive Agents; D000242:Cyclic AMP; D010627:Phenethylamines; D010660:Phenylisopropyladenosine; D010975:Platelet Aggregation Inhibitors; D058906:Purinergic P1 Receptor Agonists; D011687:Purines; D018047:Receptors, Purinergic P1; D012701:Serotonin; D013449:Sulfonamides; D013806:Theophylline; D014665:Vasodilator Agents; D014970:Xanthines; C052023:N-(2-(dimethylamino)ethyl)-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; C028322:8-phenyltheophylline