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Biomedical subjects

A H Neufeld

Publications and source records attributed to A H Neufeld.

At least 73 records · Page 4Linked to original sources
PubMed1980

Pharmacological effects of topical timolol in the rabbit eye.

The ability of timolol to act as a beta-adrenergic antagonist in the cornea and in the iris--ciliary body of albino rabbits is reported. In vitro, timolol potently blocks the isoproterenol-stimulated synthesis of cAMP. In the iris-ciliary body, the apparent inhibition constant (K1) for timolol is 0.6 nM, indicating that timolol is approximately seven times more potent than propranolol. Topical timolol (0.5% and 4%) rapidly inhibits the beta-adrenergic--stimulated synthesis of cAMP in both corneal and iris--ciliary body tissues. Within 3 hr, however, the iris--ciliary body tissue regains its ability to produce large amounts of cAMP when challenged in vitro with isoproterenol. The washout of timolol from corneal tissue is more protracted. Intraocular pressure measurements by anterior chamber cannulation of anesthetized rabbits indicate that topical timolol (0.5% and 4%) has no significant influence on intraocular pressure. These concentrations of timolol significantly decrease heart rate but do not affect femoral arterial blood pressure. Because of the marked potency of timolol clinically, we conclude that the effects of the drug in the rabbit do not completely account for its therapeutic efficacy in humans, which must depend on more complex pharmacological actions.

Adrenergic beta-Antagonists↗
PubMed1980

Cholera toxin stimulates adenosine 3',5'-monophosphate synthesis and epithelial wound closure in the rabbit cornea.

Rabbit corneas were treated in vitro and in vivo with cholera toxin (CTX), a specific and irreversible activator of adenylate cyclase. Tissue pieces incubated in vitro in the presence of 10 mug/ml CTX for 15 min continuously synthesized adenosine 3',5'-monophosphate (cyclic AMP) at an increased rate for 3 hr in the absence of CTX in the medium. Corneas exposed for 10 min to CTX topically in vivo and after various time intervals incubated in vitro had an increased ability to synthesize cyclic AMP for at least 30 hr after topical treatment. Epithelial wounds, 6 mm in diameter, were made by brief exposure of corneas in vivo to filter disks soaked in heptanol. Wounds in corneas pretreated with CTX closed at a faster rate and earlier than wounds in corneas pretreated with inactivated CTX. We postulate that cyclic AMP mediates the initial events governing the rate of closure of an epithelial defect.

Adenylyl Cyclases↗
PubMed1979

Modification by timolol of catecholamine stimulation of chloride transport in isolated corneas.

In the isolated frog cornea, 10(-5)M timolol completely blocked the stimulation of chloride transport by 10(-6)M isoproterenol. In this preraration, timolol inconsistently modified the response to epinephrine. In some experiments, epinephrine added to the bathing medium after timolol caused a smaller than normal increase in chloride transport, but in other instances, epinephrine caused a decrease in chloride transport. In the isolated rabbit cornea, 10(-5)M timolol totally blocked the stimulation of chloride transport by 10(-6)M epinephrine. In vivo, topical treatment of rabbit eyes with 0.5% timolol resulted in corneas from these eyes having an inhibited response to epinephrine when incubated in vitro. This inability to stimulate chloride transport persisted for several days following termination of topical treatment with timolol.

Administration, Topical↗
PubMed1979

The rabbit cornea lacks cholinergic receptors.

Cholinergic receptors were studied in membranes prepared from rabbit cornea, iris-ciliary body, and retina, using 3H-quinuclidinyl benzilate (3H-QNB) to identify muscarinic receptors and 125I-alpha-bungarotoxin (125I-BGT) to identify nicotinic receptors. Muscarinic cholinergic receptors were not found in the cornea. As a positive control, muscarinic cholinergic receptors were characterized in preparations of the iris-ciliary body. Specific binding of 3H-QNB to iris-ciliary body membrane preparations was saturable, with a Kd of 1.3 nM QNB. Specificity of the assay for muscarinic receptors was confirmed by the relative abilities of the following compounds to displace 3H-QNB: atropine greater than pilocarpine greater than hexamethonium. Nicotinic cholinergic receptors were not found in the cornea. As a positive control, nicotinic cholinergic receptors were characterized in preparations of the retina. Specific binding of 1252-BGT to retinal membrane preparations was saturable with both high and low affinity receptors (Kd values of 1.0 nM and 93 nM BGT, respectively). Specificity of the assay for nicotinic receptors was confirmed by the relative abilities of the following compounds to prevent 125I-BGT binding: curare greater than or equal to nicotine greater than hexamethonium greater than atropine. The lack of cholinergic receptors in the cornea, which has high levels of acetylcholine and related enzymes, suggests either an extraordinary use or a lack of function for acetylcholine in this tissue.

Animals↗
PubMed1978

Topical epinephrine causes a decrease in density of beta-adrenergic receptors and cathecholamine-stimulated chloride transport in the rabbit cornea.

A single administration, or twice daily administration for 4.5 days, of topical 2% epinephrine to the rabbit eye in vivo causes a 30-40% decrease in the density of beta-adrenergic receptors on membranes prepared from the cornea. Such treatment also causes complete loss of the ability of excised corneas to respond to epinephrine in vitro with enhanced active chloride transport. These findings indicate that stimulation with a high concentration of catecholamine depresses the entire pathway from receptor to physiological response.

Amphotericin B↗
PubMed1978

Influences on the density of beta-adrenergic receptors in the cornea and iris--ciliary body of the rabbit.

By measurement of the specific binding of 3H-dihydroalprenolol, the densities of beta-adrenergic receptors on membranes prepared from homogenized corneas and iris--ciliary bodies of rabbits were studied. Sympathetic denervation, as a result of subconjunctival treatment with 6-hydroxydopamine, causes an increase in the density of beta-adrenergic receptors in membranes prepared from the ipsilateral iris--ciliary body but not the cornea. Topical treatment with epinephrine for 5 days causes a decrease in the density of beta-adrenergic receptors in membranes prepared from cornea and iris-ciliary body, whereas similar treatment with timolol causes an increase in the density of beta-adrenergic receptors. In the cornea, the decrease in receptor density that occurs following in vivo treatment with epinephrine is associated with a decreased ability to synthesize cyclic AMP, whereas the increase in receptor density that occurs following in vivo treatment with timolol is not associated with an altered ability to synthesize cyclic AMP. Our results indicate that the density of beta-adrenergic receptors in the anterior segment of the eye is inversely related to the level of adrenergic stimulation to the tissue but that the ability of a tissue to synthesize cyclic AMP does not necessarily parallel the change in receptor density.

Animals↗
PubMed1977

In vitro determination of the ability of drugs to bind to adrenergic receptors.

Alpha- and beta-adrenergic receptors were studied by measuring the binding of 3H-dihydroergocryptine and 3H-dihydroalprenolol, respectively, to membranes prepared from homogenized rabbit iris--ciliary bodies. The binding of 3H-dihydroergocryptine appears to be specific for alpha-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: phentolamine greater than epinephrine greater than or equal to norepinephrine greater than or equal to isoproterenol = propranolol. The binding of 3H-dihydroalprenolol appears to be specific for beta-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: propranolol greater than or equal to isoproterenol greater than or equal to epinephrine greater than norepinephrine greater than or equal to phentolamine. Clonidine and dopamine bind to the alpha-adrenergic receptor but have little activity at the beta-adrenergic receptor. Timolol, d-isoproterenol, and dipivalyl epinephrine bind to the beta-adrenergic receptor but have little activity at the alpha-adrenergic receptor. The results demonstrate that in vitro binding assays for alpha- and beta-adrenergic receptors are useful for studying the mechanism of drug action.

Alprenolol↗
PubMed1976

Differential reactivity of rabbit iris and ciliary process to topically applied prostaglandin E2 (dinoprostone).

The topical application of prostaglandin E2 (dinoprostone) is followed by massive swelling of the ciliary process, leading to substantial leakage of marker dye into the posterior chamber and directly into the region of the iris, where the primary ciliary processes insert. In contrast, blood vessels of the iris proper retain most of their normal barrier quality and do not leak Evans blue dye. The adrenergic innervation of the anterior segment remains normal in density and in quality after the topical application of PGE.

Administration, Topical↗
PubMed1976

The effect of d-isoproterenol on intraocular pressure of the rabbit, monkey, and man.

D-isoproterenol d-bitartrate applied topically lowers intraocular pressure (IOP) in normal albino rabbits and rabbits with alpha-chymotrypsin-induced glaucoma. This effect is independent of any effect on systemic blood pressure or pulse rate. A similar response could not be obtained in monkey or human eyes. Subconjunctival injection of d-isoproterenol d-bitartrate to monkey eyes did not alter IOP.

Administration, Topical↗
PubMed1975

Morphology of the breakdown of the blood-aqueous barrier in the ciliary processes of the rabbit eye after prostaglandin E2.

Protaglandin E2, administered topically to the rabbit eye, causes disruption of the blood-aqueous barrier resulting in a large increase in the protein content of the aqueous humor. The route of plasma proteins into the aqueous humor was studied with the electron microscope, using horseradish peroxidase as a protein tracer. The tracer penetrated the tight junctions of the nonpigmented layer of the ciliary epithelium, filling the lateral intercellular clefts and staining the internal limiting membrane. These morphological studies confirm the prior physiologic demonstration that, in response to prostaglandin, plasma proteins enter the posterior chamber via the intercellular clefts of the nonpigmented epithelium.

Administration, Topical↗
PubMed1975

Pathways for the response of the eye to injury.

The role of a neural pathway in the disruption of the blood-aqueous barrier of the rabbit after two irritating stimuli, topical nitrogen mustard, and paracentesis, was studied. Retrobulbar anesthesia or section of the ophthalmic division of the trigeminal nerve decreased the breakdown of the blood-aqueous barrier, as measured by protein in the aqueous humor, after topical nitrogen mustard. Sensory denervation, accomplished with retrobulbar alcohol, virtually prevented the protein rise in the aqueous humor. Disruption of the blood-aqueous barrier after paracentesis, however, was not affected by retrobulbar anesthesia or alcohol denervation. Therefore, the increased protein in the aqueous humor after an irritative stimulus appears to be mediated by at least two pathways. The response to a stimulus such as nitrogen mustard depends on sensory innervation and is not mediated by prostaglandins to any important degree. The response to paracentesis does not require sensory innervation and appears to be mediated, at least in part, by prostaglandins.

Animals↗