Nicholas Brecha, PhD

Professor, Division of Digestive Diseases, Vice Chairman, Department of Neuorbiology, David Geffen School of Medicine at UCLA

Dr. Brecha studies the expression and function of neuropeptides in the peripheral and central nervous system. He currently is focusing his studies on three inhibitory peptides, neuropeptide Y, somatostatin and opioids, and their receptors. Specific studies are concerned with determining the expression of their receptors in the nervous system with an emphasis on retina and gastrointestinal tract at the cellular level. Current studies are also examining peptide modulation of intracellular calcium concentration ([Ca2+]i) and Ca2+ and K+ currents in isolated neurons using fluorometric Ca2+ imaging and patch clamp techniques. For example, Dr. Brecha and his collaborators demonstrated that somatostatin inhibits both K+ and calcium ion channels in the axonal terminals of bipolar cells and photoreceptors at low concentrations. Interestingly, these cells prominently express the somatostatin receptor subtype sst2A suggesting this action is mediated through this receptor. These investigations provide further support for a role of somatostatin in the presynaptic modulation of transmitter release from retinal cells and serve as a paradigm for understanding the regulatory functions of this neuropeptide in other tissues and organs, including the GI tract. In addition, Dr. Brecha is studying the expression of GABA plasma membrane and vesicular transporters in the nervous system, and testing their role in mediating transmitter release from neurons using fluorometric Ca2+ imaging and patch clamp techniques. To better understand the synaptic inactivation of GABA, the cellular localization of GABA uptake sites is being determined using novel cDNA probes and antibodies to the four major forms of the GABA transporter known as GAT-1, GAT-2, GAT-3 and BGT-1. The overall goal of these studies is to determine the role of neuropeptides and transmitters mediating sensory and motor function in the nervous system; his program makes a substantial contribution to the interdisciplinary activities of our Center.