The goal of this project is to discover the molecular basis of nerual regulatory mechanism in the pineal gland and to describe how the pineal gland functions. The approach is primarily biochemical and has yielded new information about pineal alpha-adrenergic receptors, how alpha-adrenergic receptors interact with beta-adrenergic receptors to control cyclic GMP, how phospholipid metabolism is involved in the control of cyclic AMP via a calcium, phospholipid-dependent protein kinase, has revealed that there are two amine N-acetyltransferases in the pineal gland, has developed new methods for the purification of pineal serotonin N-acetyltransferase and hydroxyindole-O-methyltransferase (HIOMT), has prepared antiserum against HIOMT, has prepared a bovine pineal cDNA library, and has started to screen for HIOMT clones. This project has described the development and photoneural regulation of alpha-adrenergic receptors, has described these receptors in sheep, has demonstrated that these receptors are of central importance in regulating melatonin production. A new infusion of concepts and tools into pineal research came from an active pursuit of collaborations with retinal scientists, which has led to the discovery of rhodopsin kinase in the pineal gland, the isolation of bovine S-antigen cDNA, the partial sequence of this protein, and the identification of the S-antigen in all pineal organs of all vertebrates. Perhaps the most important discovery of this program was that pinealocytes sent projections into the brain, which provided the first evidence that pineal cells of mammals may function as neurons, as do pineal cells of low vertebrates. Another activity of this project was to organize an international symposium on pineal-retinal relationships, in cooperation with the National Eye Institute.
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