Activation of adenosine A2 receptors stimulates phosphoinositide metabolism in rat peripheral nerve.
The effects of adenosine analogues on phosphoinositide metabolism in rat sciatic nerve were examined. Sciatic nerve segments were prelabeled with [3H]-cytidine and incubated in the presence of LiCl and varying concentrations of adenosine analogues. The formation of [3H]cytidine monophosphate phosphatidic acid [3H]-CMP-PA) was determined as an index of phosphoinositide breakdown. Liponucleotide accumulation was elevated significantly in the presence of 5'-N-ethylcarbox-amidoadenosine (NECA), a nonselective analogue, and two different A2-selective analogues, N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine and 2-p-(2-carboxyethyl)phenethylamino-NECA (CGS 21680), but not by N6-cyclopentyladenosine, an A1-selective analogue. The stimulatory action of CGS 21680 was blocked by the A2-selective adenosine receptor antagonists 3,7-dimethyl-1-propargylxanthine (DMPX) and 1,3-dipropyl-7-methylxanthine. Inositol phosphate formation was also stimulated to a comparable degree by CGS 21680 and this response was antagonized by DMPX. Carbamylcholine, which was previously shown to stimulate phosphoinositide breakdown, also enhanced the accumulation of CMP-PA. When adenosine analogues and carbamylcholine were simultaneously present, their effects were additive. Taken together, these data suggest that an adenosine receptor, possibly of the A2 subtype, is coupled to enhanced phosphoinositide hydrolysis in peripheral nerve. However, adenosine-receptor activation does not appear to modulate phosphoinositide hydrolysis stimulated via muscarinic receptors.
Sheldon
R L
RL
Department of Biochemical and Biophysical Sciences, University of Houston 77204-5934, USA.
Bonasera
L K
LK
Eichberg
J
J
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism; D004357:Drug Synergism; D020404:Glycerophospholipids; D066298:In Vitro Techniques; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D058913:Purinergic Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism*
D020404:Glycerophospholipids; D010627:Phenethylamines; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D058913:Purinergic Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C088379:cytidine monophosphorylphosphatidate; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D002217:Carbachol; D003568:Cytidine Monophosphate; D000241:Adenosine