Laurence Brunton Professor of Pharmacology and Medicine Ph.D., University of Virginia Phone: 858-534-4667 Fax: 858-534-6833 E-mail: lbrunton@ucsd.edu

Key Words: Transmembrane Signaling; Cyclic Nucleotides; Protein Kinases; Cardiac Myocytes, Compartmentation of Hormone Action; Hormonal Regulation of Cardiac Function

Crosstalk amongst signaling systems. Activation of the G_q pathway (by Angiotensin II, purinergic agonists, bradykinin, etc.) can accelerate cyclic AMP production. Similarly, EGF interacts with a monospanning membrane receptor but can also modulate hormone-sensitive adenylyl cyclase, an enzyme normally regulated by heptaspanning receptors. By what molecular mechanisms does such crosstalk occur?

Hormone action in heart; role of cardiac fibroblasts. We study production and effects of second messengers (cAMP, IP₃, Ca⁺⁺, NO, cGMP) in isolated purified cardiac cells emphasizing the importance of cardiac fibroblasts in cardiac hypertrophy and heart failure.

Cellular Effects of Giardia Lamblia. Collaborating with colleagues in Pathology, we are studying Ca⁺⁺ metabolism in giardia and effects of giardia on transmembrane signaling in mammalian cells. Early data suggests that giardia produce a diffusible toxin that can inhibit Gq-PLC coupling.

Recent Publications

Beavo and Brunton (2002). Cyclic Nucleotide Research-still expanding after half a century. Nature, Mol Cell Bio 3: 710-718.

Reiner, Hetsko, Meszaros, Sun, Morrison, Brunton, Gillin (2003). Calcium Signaling in Excystation of the Early-Diverging Eukaryote, Giardia lamblia. J Biol Chem 278: 2533-2540.

Ostrom, Naugle, Hase, Gregorian, Swaney, Insel, Brunton and Meszaros (2003) Angiotensin II enhances adenylyl cyclase signaling via calcium-calmodulin: Gq-Gs crosstalk regulates collagen production in cardiac fibroblasts. J Biol Chem 278: 24461-24468.

Saucerman, Brunton, Michailova, and McCulloch (2003) Analysis of face="Symbol">b-adrenergic control of cardiac myocyte contractility in silico. J.Biol Chem 278: 47997-48003.

Brunton (2003) PDE4: Arrested at the Border - Compartmentation of cAMP signaling via phosphodiesterase recruitment by face="Symbol">b-arrestin. Science stke 2003 (204), pe44.

Gustafsson and Brunton (2004). Interactions of the Cyclic AMP and Nitric Oxide Pathways in Cardiac Fibroblasts. ISHR Proceedings 2001 (Pathophysiology of Cardiovascular Disease), 109-123.

Goodman and Gilman's The Pharmacological Basis of Therapeutics (ed., LL Brunton), 11th edition, McGraw-Hill, New York, 2005, in preparation.