We have conducted studies in two distinct organ systems, the kidney and the adrenal medulla. Our renal study tests the hypothesis that NaCl homeostasis is maintained at least in part, by an entero-renal endocrine axis in which urinary NaCl excretion is rapidly regulated by two recently identified peptides, uroguanylin (UGN) and guanylin (GN), which are released from the gastrointestinal tract in response to altered NaCl intake. This work utilizes classical renal physiological techniques such as in vitro microperfusion and in vivo micropuncture, in combination with cellular and molecular biological analysis of microdissected renal tubular segments and renal epithelial cells in culture.

The long-term goal of our adrenal project is to identify factors that modulate catecholamine synthesis and secretion in adrenal medullary chromaffin cells. We are testing the hypothesis that both intrinsic and extrinsic factors can affect both processes by modulating the activity of critical signal transduction pathways including nicotinic receptor-dependent increases in intracellular calcium via voltage-gated calcium channels, and peptidergic receptor-dependent increases in intracellular cAMP. These experiments utilize diverse techniques including patch-clamp analysis of ion channels, fluorescence imaging of intracellular calcium, carbon-fiber amperometric analysis of single-cell catecholamine secretion, RT-PCR and northern blotting.