Research in my laboratory focuses on the biology of adrenal chromafin cells. Chromaffin cells secrete the catecholamine hormones epinephrine and norepinephrine, and a variety of other neuropeptides including enkephalin. Chromaffin cells are classical neuroendocrine cells: they receive synaptic inputs from other neuronal cells, they depolarize and generate action potentials in response to synaptic stimulation, and they release their stored secretory materials in response to this depolarization. Because they represent a relatively homogeneous cell population that can be isolated in large numbers, chromaffin cells have served as an important model system for studies of neuronal function. Much of our knowledge about the mechanisms of neurotransmitter release--that transmitters are stored in secretory vesicles, that release is Ca2 +-dependent, and that release occurs by exocytosis--has come from studies on chromaffin cells. We are interested in the signal transduction mechanisms by which neurotransmitters, hormones, and growth factors regulate chromaffin cell function. We study the interactions of these agents with receptors on chromaffin cells, the regulation of enzymes and ion channels by these receptors, and the generation of intracellular signals in response to receptor activation. We also study protein phosphorylation and gene expression as common pathways for the short-term and long-term modulation of cell function. There are two types of chromaffin cells; some cells (adrenergic cells) secrete norepinephrine. We are studying the properties of these two chromaffin cell subtypes in order to understand the mechanisms that underlie the selective release of epinephrine or of norepinephrine from the adrenal medulla. We are especially interested in the expression of receptors for secretory stimuli on adrenergic and noradrenergic cells, since receptor density appears to be a major determinant of the responses of these cells to secretory stimulation. We are also studying the effects of glucocorticoids on gene expression in adrenergic and noradrenergic cells. Glucocorticoids increase expression of the enzyme phenylethanolamine N-methyltransferase, the enzyme that converts norepinephrine to epinephrine, and thus may convert noradrenergic cells into adrenergic cells. We are interested in the plasticity of chromaffin cells and in the extent to which their phenotype can be modulated by glucocorticoids. In other research, carried out in collaboration with Aaron Fox, we are studying the regulation of Ca2 + channel function in chromaffin cells. The adrenal medulla plays a central role in the maintenance of homeostasis and in the response to stress. Our studies will increase our understanding of the biochemical mechanisms that enable the adrenal medulla to carry out these important physiological functions.