The human and mouse synexin genes were sequenced, and assigned to homologous chromosomes. The human gene was located at position 10q21.1- 21.2, while the mouse gene was located on chromosome homologous 14. The synexin genes were found to be highly homologous in terms of splice junction location, but quite distinct from the organization of other members of the annexin family. The half life of synexin was found to be ca. 40 h, and inhibitors of protein synthesis blocked secretion from bovine chromaffin cells in an appreciably shorter time. Thus, in addition to synexin other proteins are required for the secretory process. Human cytochrome b 561, a major transmembrane protein of chromaffin granules, was found to have 5 transmembrane domains rather than the six previously hypothsized. membrane potential was found to regulate cytoplasmic calcium oscillations in pituitary gonadoptrophs. M3-muscarinic receptors were found to potentiate glucose-induced insulin release from rat islets. The diabetogenic agent alloxan was found to activate K (ATP) channels in mouse pancreatic beta cells. A novel, cerebrospinal/vascular shunt was developed to implant xenobiotic islets in diabetic animals. Human pancreatic islets were analyzed by electrophysiologic methods for the first time. Evidence was obtained that 1CRAC currents control electrical activity in islets through effects on cholinergic receptors. A geometric sequence (the three-halves rule) was developed which accurately describes allowed multiple conductance states of ion channels. A theoretical model of the ion channel structure of the amyloid beta protein was constructed. A xanthine drug (CPX) and an analog compound (DAX) were found to activate chloride efflux from cystic fibrosis cells. An IND was filed with the FDA and clinical testing is planned. Uptake of ascorbate and dehydroascorbate were found to be taken up by fibroblasts by separate mechanisms.
