We are interested in signal transduction systems in the heart and use embryonic chick cardiac myocytes as our primary model system. Our focus for a number of years has been on cardiac adenosine receptors with regards to their role in normal cardiac function, and more recently, cardiac preconditioning. We have cloned the chick A1 and A3 adenosine receptors which are expressed in the heart and are currently using heterlogous expression systems to study the signal transduction pathways by which these receptors modulate cardiac function, and is situ hybridization techniques to determine the distribution of these receptros in the heart. Serveral years ago we found that elevations in cAMP lead to increases in intracellular Ca2+ that feedback to inhibit the production of cAMP and shifted our interests to include studies on the roles of different cardiac adenylyl cyclase (AC) isozymes in the control of cardiac cAMP and the control mechanisms that modulate the activities of the individual AC isozymes. To date we have partially cloned the two primary AC isozymes expressed in chick myocytes, and made polyclonal antibodies directed toward theses isozymes. These antibodies will be used in studies to study the role of phosphorylation in the control of the activities of these isozymes. We have also shown that recombinant human adenoviruses can be used to express foreign proteins in chick myocytes and plan to study the contributions of the various cardiac. AC isozymes to cardiac function using adenoviruses and antisense technology. The object of these experiments is to more fully understand interactions between cAMP and Ca2+ in the heart.
Publications:
1. Ma, H. and Green, R.D.: Modulation of cardiac cAMP metabolism by adenosine receptor agonists and antagonists. Mol. Pharmacol. 42:831-837, 1992.
2. Yu, H.J., Ma, H. and Green, R.D.: Calcium entry via L-type calcium channels acts as a negative regulator of adenylyl cyclase activity and cMP levels in cardiac myocytes. Mol Pharmacol. 44:689-693, 1993.
3. Ma, H., Yu, H.J. and Green, R.D.: Adenosine receptor-mediated inhibition of cardiac adenylyl cyclase activity may involve multiple receptor subtypes. Naunyn-Schmiedeberg's Arch. Pharmacol. 349:81-86, 1994.
4. Aguilar, J.S., Tan, F., Durand, I, and Green, R.D.: Isolation and characterization of an avian A1 adenosine receptor gene and a related cDNA clone. Bioch. J.307:729-734, 1995.
4. Yu, H.J., Unnerstall, J.R., and Green, R.D.: Determination and cellulr localization of Adenylyl cyclase isozymes expressed in embryonic chick heart. FEBS Letters374:89-94, 1995.