The steady state level of phosphorylated intermediate in relation to the two sodium-dependent adenosine triphosphatases of calf brain microsomes.
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Adenosine Triphosphatases↗
Biomedical subjects
A H Neufeld
Publications and source records attributed to A H Neufeld.
A second ouabain-sensitive sodium-dependent adenosine triphosphate in brain microsomes.
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Adenosine Triphosphatases↗
Experimental studies on the mechanism of action of timolol.
Timolol, which binds to beta-adrenergic receptors, is a potent antagonist of the catecholamine-stimulated synthesis of cyclic AMP. However, the actual mechanism of action by which timolol reduces intraocular pressure is not readily apparent. Compared to its efficacy in human eyes, the drug is relatively ineffective in rabbit eyes. A reasonable postulate is that soon after administration, timolol blocks endogenous adrenergic stimulation contributing to the formation of aqueous humor by the ciliary processes. Nevertheless, the long-lasting reduction of intraocular pressure persists at a time when the drug is no longer bound to beta-adrenergic receptors.
Animals↗
Forskolin stimulates cyclic AMP synthesis, lowers intraocular pressure and increases outflow facility in rabbits.
The intracellular pathway by which beta-adrenergic agonists and antagonists affect aqueous humor dynamics involves the intracellular mediator, cyclic AMP. We have therefore tested the activity of forskolin, a direct activator of adenylate cyclase, in rabbits. Following a 15 min in vitro incubation in the presence of forskolin (15 microM) and isobutylmethylxanthine, a 10 fold increase in cyclic AMP was found in both rabbit iris-ciliary body and scleral-trabecular rings relative to controls. Following an intracameral injection of forskolin (10 micrograms) a time-dependent decrease in intraocular pressure was observed, which reached a mean decrease of 5 mm Hg at 4 hr in unanesthetized rabbits. Outflow facility was measured in anesthetized rabbits by constant pressure perfusion before injection and 1 hr after injection of either forskolin (10 micrograms) or control vehicle. Forskolin caused an approximate doubling of outflow facility (0.41 microliter/min/mm Hg) compared to the preinjection mean value. Control vehicle, ethyl alcohol, caused a statistically insignificant increase in outflow facility. At this concentration of forskolin, the integrity of the blood-aqueous barrier was normal as measured by protein and fluorescein entry into the aqueous humor. These results indicate that agents which directly activate adenylate cyclase are effective at increasing outflow facility and decreasing IOP.
Adrenergic beta-Agonists↗