Purinergic regulation of bradykinin-induced plasma extravasation and adjuvant-induced arthritis in the rat.
We assessed the contribution of ATP and adenosine (i) to a major sign of acute inflammation, plasma extravasation (PE), in the rat knee joint and (ii) to the severity of joint injury in adjuvant-induced experimental arthritis, a chronic inflammatory disease. PE induced by local infusion of bradykinin, which we have previously shown to depend on the sympathetic postganglionic neuron terminal, was markedly enhanced by coinfusion of either ATP or the adenosine A2-receptor agonist 2-[4-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine. Bradykinin-induced PE was inhibited by coinfusion of the ATP receptor antagonist adenosine 5'-[alpha,beta-methylene]triphosphate, the A2-receptor antagonist 3-(5H-thiozolo[2,3b]quinazolin-3-yl)phenol monohydrochloride, or the adenosine A1-receptor agonist N6-cyclopentyladenosine. The joint injury associated with experimental arthritis, which is reduced in severity in sympathectomized rats, was also markedly attenuated by daily administration of either ATP (40% reduction) or adenosine (55% reduction). These results demonstrate that the purines ATP and adenosine (acting at the A2 receptor), cotransmitters in the sympathetic postganglionic neuron terminal, enhance bradykinin-induced sympathetic postganglionic neuron terminal-dependent PE but inhibit the joint injury of arthritis. These opposing purinergic effects on PE and joint injury suggest that enhanced PE protects against joint injury.
Green
P G
PG
Department of Medicine, University of California, San Francisco 94143.
Basbaum
A I
AI
Helms
C
C
Levine
J D
JD
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001168:Arthritis / Q000139:chemically induced*; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001920:Bradykinin; D007719:Knee Joint; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010627:Phenethylamines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000255:Adenosine Triphosphate; D000241:Adenosine; D001920:Bradykinin