Activation of a metabotropic excitatory amino acid receptor potentiates A2b adenosine receptor-stimulated cyclic AMP accumulation.
Incubation of guinea-pig cerebral cortical slices with the excitatory amino acid agonists DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) or N-methyl-D-aspartate (NMDA) failed to significantly alter either basal or 5'-N-ethylcarboxamidoadenosine- (NECA-)stimulated cAMP levels. Quisqualate, L-glutamate and DL-1-aminocyclopentane-trans-1,3- dicarboxylate (t-ACPD) were also without effect on basal levels of cAMP but increased NECA-stimulated levels of cAMP to approximately 190, 220 and 290% of control levels, respectively. Analysis of t-ACPD concentration-response data for the potentiation of NECA-stimulated cAMP elevations and the stimulation of phosphoinositide turnover gave EC50 values of 51 and 107 microM, respectively. The enhancing effect of t-ACPD on cAMP levels was maintained for up to 40 minutes as was the stimulation of phosphoinositide turnover. We conclude that the cAMP response to A2b adenosine receptor stimulation is augmented by the rigid glutamate analogue t-ACPD, possibly through the action of products of phosphoinositide turnover.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001711:Biotransformation / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D017459:Receptors, Amino Acid / Q000187:drug effects / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007295:Inositol Phosphates; D017459:Receptors, Amino Acid; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D007051:Ibotenic Acid; D019830:Adenosine-5'-(N-ethylcarboxamide); D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000242:Cyclic AMP; D000241:Adenosine