Abstract

I propose to investigate the mechanisms by which vasoconstrictor hormones (angiotensin II, vasopressin, Alpha-adrenergic agents) stimulate calcium and prostaglandin (PG) biosynthesis in cultured rat mesenteric arterial smooth muscle and endothelial cells. The following are specific questions to which answers may be elicited: a) Do vasoconstrictors alter cytosolic calcium levels in cultured cells as measured directly by photoprotein luminescence or fluorescence of intracellular organic calcium indicators? b) What is the role of intracellular and extracellular calcium in hormone-evoked PG biosynthesis? c) What are the effects of vasoconstrictors on the metabolism of phosphatidylinositol, phosphatidic acid and polyphosphoinositides? What is the role of calcium in mediating these changes? d) Does phosphatidic acid function as an endogenous cellular calcium ionophore? e) Do polyphosphoinositides function as endogenous intracellular calcium stores? We expect to use the following analytical techniques to achieve our goals: radioimmunoassay of PGs, measurement of intracellular calcium by a novel technique of aequorin luminescence (or alternatively, measurement of intracellular calcium with the aid of intracellular fluorescent calcium indicators), transmembrane flux of radio-active calcium and radiometric thin-layer chromatography of phospholipids. The results obtained from this research program may increase our understanding of the role played by phospholipids in regulating calcium channels and of the role played by calcium in regulating PG biosynthesis and vasoconstriction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033769-02
Application #
3345946
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1984-09-01
Project End
1987-07-31
Budget Start
1985-09-01
Budget End
1987-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Tennessee Health Science Center
Department
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163

  Publications

Cahill, P A; Hassid, A (1993) Differential antimitogenic effectiveness of atrial natriuretic peptides in primary versus subcultured rat aortic smooth muscle cells: relationship to expression of ANF-C receptors. J Cell Physiol 154:28-38
Garg, U C; Hassid, A (1993) Mechanisms of nitrosothiol-induced antimitogenesis in aortic smooth muscle cells. Eur J Pharmacol 237:243-9
Lermioglu, F; Goyal, J; Hassid, A (1991) Cell density modulates the decrease of cytosolic free Ca2+ induced by atrial natriuretic hormone, S-nitroso-N-acetylpenicillamine and 8-bromo cyclic GMP in cultured rat mesangial cells. Biochem J 274 ( Pt 2):323-8
Garg, U C; Hassid, A (1991) Nitric oxide decreases cytosolic free calcium in Balb/c 3T3 fibroblasts by a cyclic GMP-independent mechanism. J Biol Chem 266:9-12
Songu-Mize, E; Bealer, S L; Hassid, A I (1990) Centrally administered ANF promotes appearance of a circulating sodium pump inhibitor. Am J Physiol 258:H1655-9
Garg, U C; Hassid, A (1990) Nitric oxide-generating vasodilators inhibit mitogenesis and proliferation of BALB/C 3T3 fibroblasts by a cyclic GMP-independent mechanism. Biochem Biophys Res Commun 171:474-9
Garg, U C; Hassid, A (1989) Inhibition of rat mesangial cell mitogenesis by nitric oxide-generating vasodilators. Am J Physiol 257:F60-6
Garg, U C; Hassid, A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83:1774-7
Hassid, A; Yu, Y M (1989) Mechanism of atriopeptin-induced decrease of cytosolic free Ca in rat vascular smooth muscle cells: evidence for an intracellular locus of action. J Cardiovasc Pharmacol 14 Suppl 6:S34-8
Yu, Y M; Lermioglu, F; Hassid, A (1989) Modulation of Ca by agents affecting voltage-sensitive Ca channels in mesangial cells. Am J Physiol 257:F1094-9

Showing the most recent 10 out of 18 publications