ABSTRACT IBN 9604516 LEISE Neurotransmitters are typically small molecules that are released by an activated nerve cell, allowing it to communicate with other neurons. Most neurotransmitters are stored within vesicles and released for short periods of time when a neuron is electrically excited. Upon release, these molecules diffuse across a narrow synaptic cleft and interact with surface receptors on their target cells. In the last 15 years, a new class of neurotransmitters has been identified that acts in a different fashion. These gaseous neurotransmitters, including nitric oxide and carbon monoxide, are made enzymatically upon demand, and can diffuse through cells and tissues to interact with intracellular biochemical pathways. Of these two gases, more is known about the functions of nitric oxide and how it acts in adult nervous systems. For example, nitric oxide plays roles in systems as diverse as behavioral aggression, learning and memory, and the mediation of olfactory responses. The functions of this molecule in developing nervous systems are, however, still being elucidated. Preliminary data from Dr. Leise's research have indicated that nitric oxide may act within developing nervous systems as a natural inhibitor of metamorphosis. Upon release, nitric oxide typically interacts with the enzyme guanylyl cyclase to enhance production of the intracellular messenger molecule cGMP, which in turn can affect a broad range of cellular biochemistry. To determine if the typical nitric oxide-guanylyl cyclase pathway is part of the cellular systems that control metamorphosis, Dr. Leise and her coworkers will conduct a series of related experiments on a species of marine snails. They will use pharmacological experiments to block the production of nitric oxide, which should allow metamorphosis to proceeed. They will use biochemical assays to measure levels of cGMP before, during and after metamorphosis, and they will also use immunocytochemical procedures to determine which cells prod uce nitric oxide and which cells are the likely targets that contain the enzyme guanylyl cyclase. These investigations will determine whether or not nitric oxide plays an important role in governing the onset of metamorphosis. Even humans retain vestiges of metamorphosis in the hormonal changes that we undergo during puberty, and it may be that this new gaseous neurotransmitter plays a role in this important developmental process.
