| Grant number: | 96/04497-0 |
| Support Opportunities: | Research Projects - Thematic Grants |
| Start date: | October 01, 1996 |
| End date: | May 31, 2000 |
| Field of knowledge: | Biological Sciences - Pharmacology |
| Principal Investigator: | Regina Pekelmann Markus |
| Grantee: | Regina Pekelmann Markus |
| Host Institution: | Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| City of the host institution: | São Paulo |
Abstract
Melatonin, the hormone released during the dark phase of the light-dark cycle is an important synchronizer of phsyiological conditions to enviromental light. We are interested in studying mechanism of neurotransmission in the pineal gland, and importance of melatonin in the regulation of neurtransmission and inflammation. 1) PURINOCEPTORS AND PINEAL FUNCTION - We have shown previously that rat pineal glands has P2 purinoceptors that could modulate pineal metabolism. Presently, through the measurement of cAMP, cGMP, [Ca]i, after stimulation of rat pineal glands or pinealocytes in culture with several purinergic agonists, we are classifying the purinoceptors. The relevance of purinergic neurotransmission for pienal function will also be analysed. 2) CIRCADIAN VARIATION OF CHRONIC INFLAMMATION - We have shown that paw chronic edema induced by BCG injection in mice hind-paws presents a circadian variation that is due to melatonin released by the pineal gland. Our goal is look for the mechanism of action of melatonin by evaluating the vascular permeability and the effect of melatonin on macrophage NO synthase activity, cGMP level and PGE2. On the other hand, the effect of melatonin on cultured endothelial cells are also being evaluated. 3) MELATONIN AND THE MODULATION OF NEURONAL NICOTINIC CHOLINOCEPTORS (nAChRs). - We have shown previously that the activity and the number of nAChRs present in short adrenergic neurones that innervate the rat vas deferens presents a circadian variation due to the nocturnal release of melatonin by the pineal gland. The effect of melatonin is dependent on protein synthesis. The aim of the present project is to extend those observation to the central nervous system (hippocampus and cerebellum), where the pharmacological characterization of nAChRs by binding assays, as well as, the physiological response, evaluated by release of neurotransmitters are being studied in preparations obtained in different hours of the day, or obtained from pinealectomized animals treated or not with melatonin. (AU)
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