The overall objective of this project continues to be an understanding of the prejunctional mechanisms that control sympathetic neurotransmission in the anterior segment of the eye. Agents that modify sympathetic neurotransmitter release have potential usefulness in glaucoma therapy. In rabbit studies, we have identified a variety of prejunctional inhibitory and facilitatory receptors that modulate norepinephrine secretion in the isolated, superfused iris-ciliary body and excised ciliary processes. We will determine, in each case, whether a pharmacological basis exists for selective manipulation of prejunctional or postjunctional uveal receptors of the same type. We will evaluate the hypothesis that prejunctional inhibitory receptors of different types share a common mechanism - decreased cAMP formation - for inhibition of norepinephrine release. The role of GTP-binding (G) proteins in receptor-mediated regulation of neurosecretion and/or adenylate cyclase will be evaluated and correlated. Using newly developed in vitro techniques, we will identify and characterize prejunctional receptors that modulate sympathetic neurosecretion in the human iris and ciliary body. The results of these studies will improve our knowledge of the pharmacologically accessible targets for regulation of sympathetic neurotransmission in the eye, and will establish their potential relevance to human ocular pharmacology, particularly with regard to glaucoma therapy.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005246-14
Application #
2159368
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1987-09-01
Project End
1998-08-31
Budget Start
1996-09-01
Budget End
1998-08-31
Support Year
14
Fiscal Year
1996
Total Cost
Indirect Cost
Name
University of Louisville
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Jumblatt, J E (1994) Prejunctional alpha 2-adrenoceptors and adenylyl cyclase regulation in the rabbit iris-ciliary body. J Ocul Pharmacol 10:617-21
Jumblatt, J E; Hackmiller, R C (1994) M2-type muscarinic receptors mediate prejunctional inhibition of norepinephrine release in the human iris-ciliary body. Exp Eye Res 58:175-80
Ohia, S E; Jumblatt, J E (1993) Prejunctional receptors and second messengers for angiotensin II in the rabbit iris-ciliary body. Exp Eye Res 57:419-25
Liu, J H; Jumblatt, J E (1993) Neuromodulatory effect of sulprostone on the circadian elevation of intraocular pressure in rabbits. Curr Eye Res 12:975-80
Jumblatt, J E; Ohia, S E; Hackmiller, R C (1993) Prejunctional modulation of norepinephrine release in the human iris-ciliary body. Invest Ophthalmol Vis Sci 34:2790-3
Ohia, S E; Jumblatt, J E (1991) Prejunctional prostaglandin receptors in the human iris-ciliary body. Curr Eye Res 10:967-75
Ohia, S E; Jumblatt, J E (1990) Prejunctional inhibitory effects of prostanoids on sympathetic neurotransmission in the rabbit iris-ciliary body. J Pharmacol Exp Ther 255:11-6
Jumblatt, J E; Gooch, J M (1990) Neuropeptide Y modulates adenylate cyclase in the rabbit iris ciliary body and ciliary epithelium. Exp Eye Res 51:229-31
Ohia, S E; Jumblatt, J E (1990) Inhibitory effects of neuropeptide Y on sympathetic neurotransmission in the rabbit iris-ciliary body. Neurochem Res 15:251-6
Jumblatt, J E; Hackmiller, R C (1990) Potentiation of norepinephrine secretion by angiotensin II in the isolate rabbit iris-ciliary body. Curr Eye Res 9:169-76

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