Application for an ADAMHA RSDA award, Level II. This proposal describes aspects of research into the mechanism of action of opiates and opioid peptides at the cellular level and also their effects on the gastrointestinal system. Opiates have been shown to regulate electrolyte transport across the intestinal mucosa at both local sites and via the central nervous system. From a broader perspective, opioids are one of a family of neurotransmitters and hormones which have been shown to regulate mucosal electrolyte transport. Experiments are proposed to further investigate the mucosal actions of opiates and opioid peptides. The antisecretory actions of opiates against a variety of secretory stimuli will be examined. Electrophysiological studies examining the effects of opioids on submucous neurones are also proposed. The role of the central nervous system in mediating opioid effects on the gastrointestinal system will be investigated. Studies on the mechanism of action of several other regulators of electrolyte transport including, kinins, icosanoids and acetylcholine are also described. In a second series of studies, the ability of opiates to regulate neuronal (Ca+2)will be examined. This is part of a group of experiments investigating in Ca+2 regulation and voltage sensitive calcium channels in single cultured neuronal cells using a microspectrofluorometer designed for the purpose. The Ca+2 sensitive fluorescent probe, quin-2 will be used in these studies. The candidates future research plans are also described including a proposed period of training in molecular biophysics.
