Biomedical subjects

J Cartmell

Publications and source records attributed to J Cartmell.

21 records · Page 2Linked to original sources

PubMed1993

Subtypes of metabotropic excitatory amino acid receptor distinguished by stereoisomers of the rigid glutamate analogue, 1-aminocyclopentane-1,3-dicarboxylate.

The 1R,3R- and 1R,3S-isomers of 1-aminocyclopentane-1,3-dicarboxylate (ACPD) failed to stimulate phosphoinositide turnover or modify A2b adenosine receptor-stimulated cyclic AMP accumulation in guinea-pig cerebral cortical slices. In contrast, both 1S,3R- and 1S,3S-ACPD elicited concentration-dependent stimulations of phosphoinositide turnover (EC50 values 35 and 97 microM, respectively) and potentiated A2b-stimulated cAMP formation (17 and 58 microM, respectively). When forskolin was used to elevate cyclic AMP levels, however, all four isomers elicited concentration-dependent inhibitions of cyclic AMP formation to the same extent (approximately 90% inhibition). For this response the rank order of potencies were (IC50 values): 1S,3S-(0.9 microM) > 1S,3R-(2.1 microM) > 1R,3R-(237 microM) > 1R,3S-ACPD (approximately 1 mM). These data suggest the presence in guinea-pig cerebral cortex of two distinct subtypes of ACPD receptor coupled to phosphoinositide hydrolysis (and the potentiation of A2b receptor-stimulated cAMP formation) and the inhibition of forskolin-stimulated cAMP accumulation. Furthermore, our results indicate the usefulness of 1S,3S-ACPD as a tool to selectively activate one of these subtypes.

Adenosine↗

PubMed1993

Endogenous adenosine regulates the apparent efficacy of 1-aminocyclopentyl-1S,3R-dicarboxylate inhibition of forskolin-stimulated cyclic AMP accumulation in rat cerebral cortical slices.

In rat cerebral cortical slices, the 1-aminocyclopentyl-1S,3R-dicarboxylate (1S,3R-ACPD) isomer of the selective metabotropic excitatory amino acid agonist ACPD inhibited forskolin-stimulated cyclic AMP (cAMP) accumulation in a concentration-dependent manner with a maximal inhibition of 51 +/- 3% and a half-maximally effective concentration of 8.8 +/- 3.4 microM. Similarly, 1R,3S-ACPD inhibited the forskolin response in a concentration-dependent manner, but with an inhibition of 80 +/- 5% at 3 mM. In addition to inhibiting forskolin-stimulated cAMP levels, 1S,3R-ACPD, but not 1R,3S-ACPD, enhanced the cAMP response to A2b adenosine receptor activation. In the presence of 1.2 U/ml of adenosine deaminase (included to reduce the contribution of endogenous adenosine), the efficacy of 1S,3R-ACPD was increased (88 +/- 3% inhibition), but the potency was unchanged. The adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine also increased the inhibitory effect of 100 microM 1S,3R-ACPD, from 57 +/- 1 to 78 +/- 5%. These results indicate that endogenous adenosine plays an important role in regulating the apparent efficacy of 1S,3R-ACPD inhibition of forskolin-stimulated cAMP accumulation in rat cerebral cortical slices and that previous studies in rat hippocampus and hypothalamus in the absence of added adenosine deaminase may have underestimated the efficacy of this compound.

Adenosine↗

PubMed1992

Inhibition of forskolin-stimulated cyclic AMP formation by 1-aminocyclopentane-trans-1,3-dicarboxylate in guinea-pig cerebral cortical slices.

The effects of the selective metabotropic glutamate receptor agonist 1-aminocyclopentane-trans-1,3-dicarboxylate (t-ACPD) on forskolin-stimulated cyclic AMP formation in guinea-pig cerebral cortex slices were determined. t-ACPD inhibited the accumulation of [3H]cyclic AMP by approximately 80%, with an IC50 value of 35 +/- 4 microM. The effect was reversible and stereoselective, with the 1S,3R isomer being approximately 400-fold more potent than the 1R,3S isomer. L-Glutamate (over a restricted concentration range) also partially inhibited the response to forskolin, but quisqualate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and N-methyl-D-aspartate (NMDA) were ineffective. The effect of t-ACPD was not blocked by antagonists of the phospholipase C-linked metabotropic glutamate receptor, the AMPA ionotropic glutamate receptor, or the NMDA receptor. In summary, our results indicate the presence of a glutamate receptor in guinea-pig brain that is activated selectively by t-ACPD and that is negatively linked to adenylyl cyclase.

Amino Acids↗