The effects of (R)-N-(1-methyl-2-phenylethyl) adenosine (L-PIA), a standard A1-selective adenosine agonist on rat acute models of inflammation and neutrophil function.
L-PIA, a standard A1-selective adenosine agonist, was evaluated orally in carrageenan (CRG)- and reverse passive arthus-pleurisy. White blood cell (WBC) and exudate accumulation were assessed four hours after induction of the inflammatory response. L-PIA inhibited WBC accumulation in both models with ID50's of 4.37 and 4.42 mg/kg, respectively. In contrast, exudate was inhibited by L-PIA only in the CRG pleurisy model (ID50 = 1.01 mg/kg). In mechanistic studies, L-PIA reversed the drop in circulating neutrophil count which occurred within 15 minutes after CRG injection, suggesting that L-PIA may inhibit adhesion of the cells to the endothelium. The effects of L-PIA on several parameters of rat neutrophil function were determined. Enzyme release, O2-, TXB2, and LTB4 production were monitored in response to FMLP and opsonized zymosan (SOZ) stimulation. At high concentrations, L-PIA had a mild inhibitory effect on O2- release in response to FMLP and had a moderate effect on arachidonic acid metabolite production in response to both stimuli. The other response were unaffected. These results suggest that L-PIA may prevent diapedisis or neutrophil adhesion to the endothelium, but has a minimal effect on enzyme release, O2-, LTB4 and TXB2 production.
Lesch
M E
ME
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Ferin
M A
MA
Wright
C D
CD
Schrier
D J
DJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001183:Arthus Reaction / Q000188:drug therapy; D002351:Carrageenan / Q000494:pharmacology; D005122:Exudates and Transudates / Q000166:cytology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D013929:Thromboxane B2 / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011983:Receptors, Purinergic; C047235:N-(1-methyl-2-phenylethyl)adenosine; D013929:Thromboxane B2; D002351:Carrageenan; D000241:Adenosine