Abstract

It is the aim of this proposal to investigate the possible biochemical mechanisms which underlie the adrenergic regulation of the tissues of the blood-brain barrier (microvasculature) and blood-CSF barrier (choroid plexus). The research will utilize biochemical and pharmacological techniques applied to isolated tissue preparations, cell suspensions, and cell culture preparations, some of which were developed in our laboratory over the past three years. These techniques will allow us to determine, in vitro, the effects of adrenergic agents on various transport (e.g., Na+, K+ fluxes) and enzymatic processes (e.g., carbonic anhydrase; ATPase; protein kinase) in cerebral vascular endothelium and choroid plexus epithelium. They will also be used to investigate certain other possible regulators of barrier function, such as vasopressin. We hope to acquire information that will improve our understanding of cerebral edema and hydrocephalus as well as the mechanisms by which drugs and nutrients gain access to the brain.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016356-06
Application #
3396843
Study Section
Neurology A Study Section (NEUA)
Project Start
1980-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code

  Publications

Wijdicks, E F; Ropper, A H; Hunnicutt, E J et al. (1991) Atrial natriuretic factor and salt wasting after aneurysmal subarachnoid hemorrhage. Stroke 22:1519-24
Wijdicks, E F; Ropper, A H; Nathanson, J A (1990) Atrial natriuretic factor and blood pressure fluctuations in Guillain-Barre syndrome. Ann Neurol 27:337-8
Gabriel, S M; Milbury, C M; Alexander, S M et al. (1989) Iso stimulation of GH and cAMP: comparison of beta-adrenergic- to GRF-stimulated GH release and cAMP accumulation in monolayer cultures of anterior pituitary cells in vitro. Neuroendocrinology 50:170-6
Nathanson, J A; Chun, L L (1989) Immunological function of the blood-cerebrospinal fluid barrier. Proc Natl Acad Sci U S A 86:1684-8
Nathanson, J A; Hunnicutt, E J (1988) Selective beta 2-adrenoceptor antagonists: derivatives of ICI 118,551 and a binary aryloxypropanolamine. J Pharm Pharmacol 40:803-5
Tapia-Arancibia, L; Pares-Herbute, N; Astier, H et al. (1988) Adenylate cyclase activation is not sufficient to stimulate somatostatin release from dispersed cerebral cortical and diencephalic cells in glia-free cultures. Brain Res 450:101-10
Gabriel, S M; Milbury, C M; Nathanson, J A et al. (1988) Galanin stimulates rat pituitary growth hormone secretion in vitro. Life Sci 42:1981-6
Nathanson, J A (1988) Direct application of a guanylate cyclase activator lowers intraocular pressure. Eur J Pharmacol 147:155-6
Nathanson, J A (1988) Stereospecificity of beta adrenergic antagonists: R-enantiomers show increased selectivity for beta-2 receptors in ciliary process. J Pharmacol Exp Ther 245:94-101
Steardo, L; Nathanson, J A (1987) Brain barrier tissues: end organs for atriopeptins. Science 235:470-3

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