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H McIntosh

Publications and source records attributed to H McIntosh.

At least 37 records · Page 2Linked to original sources

Characterization of adenosine A2 receptors in bovine retinal membranes.

Two classes of extracellular receptors for adenosine, A1 and A2, have been demonstrated in the mammalian retina. Our laboratory has previously reported the pharmacological characteristics of the mammalian retinal A1 receptors. We now report our characterization of retinal A2 receptors based on data obtained from both adenylate cyclase assays and radioligand binding studies. [3H]-5'-N-ethylcarboxamidoadenosine (NECA) in the presence of 10 nM cyclopentyladenosine (CPA, which selectively binds to A1 receptors) or [3H]-CGS 21680 were used to label the A2 binding sites. Using [3H]-NECA (plus CPA), two populations of binding sites, having Kds of 106 nM and 9.4 microM, were determined. [3H]-CGS 21680, a derivative of NECA which has been demonstrated to be highly selective for A2 receptors in brain synaptic membrane preparations was more potent than NECA at the higher affinity population of A2 sites, and saturation analysis revealed the presence of both a high affinity site, Kd of 18 nM, and a lower affinity site having a Kd of 4.3 microM. The high affinity site labeled by [3H]-CGS 21680 corresponds to the A2a receptor. Using either radioligand, guanosine triphosphate-dependent shifts to a single population of binding sites were observed. Despite the differences in affinities revealed by the two radioligands for the high affinity A2 site, both [3H]-CGS 21680 and [3H]-NECA were competitively displaced by increasing concentrations of a variety of adenosine receptor agonists and antagonists, and exhibited an identical rank order of potency that is consistent with that reported for high affinity A2a receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine↗

Muscarinic receptor stimulated GTPase activity in synaptic membranes from bovine retina.

GTPase activity has been measured in synaptic membranes from bovine retina, with and without muscarinic receptor stimulation. Maximal stimulation above basal levels was achieved with 5 microM oxotremorine and 100 microM carbachol. (4-Hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride, which is selective for the M1 muscarinic receptor, failed to stimulate GTPase activity. 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) inhibition of oxotremorine stimulation demonstrated the presence of two populations of receptors, a low-affinity site (IC50 +/- SEM, 0.63 +/- 0.18 microM) which accounted for 63% of the inhibition and a high-affinity site (IC50 less than 1 nM) which accounted for the remaining 37%. When carbachol-stimulated GTPase activity was assayed, a single 4-DAMP inhibitory site was apparent (IC50 +/- SEM, 2.0 +/- 0.9 microM). Pirenzepine inhibited GTPase activity at a single site (IC50 values +/- SEM, 46.9 +/- 11 and 25.4 +/- 6.5 microM against oxotremorine and carbachol, respectively). Methoctramine was equipotent against carbachol and oxotremorine stimulation (IC50 values, 4.2 +/- 1.8 and 6.2 +/- 1.5 microM). Inhibition of maximal carbachol and oxotremorine stimulation by muscarinic antagonists at the major site had a rank order of potency of 4-DAMP = methoctramine greater than pirenzepine. Thus, the major site for muscarinic stimulation of GTPase activity in bovine retinal membranes is pharmacologically similar to M2 receptors.

Animals↗

GAP-43-like immunoreactivity in the adult retina of several species.

The localization of GAP-43-like immunoreactivity has been determined in retinas from adult toad, snake, rat, rabbit, cow and human. Specific labeling was conspicuous in discrete sublaminae within the inner plexiform layer of all mammalian species tested. In contrast, the toad retina exhibited punctate labeling in the outer plexiform layer, while the snake retina had little or no GAP-43-like immunoreactivity.

Adult↗