Transplanted deferent duct as model for the pharmacological study of sympathetic transmission in denervation and renervation

• Grant number: 95/09432-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: August 01, 1996
• End date: July 31, 1999
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Aron Jurkiewicz
• Grantee: Aron Jurkiewicz
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant(s): 99/05783-4 - Irina Vladimirova | Bogomoletz Institute of Physiology - Ucrânia, AV.EXT; 98/04689-1 - Ageing changes Calcium signaling by muscarinic receptors in rat jejunum, AR.EXT; 96/12327-7 - Michael Shuba | Bogomoletz Institute of Physiology - Ucrânia, AV.EXT; 97/01775-1 - Effects of apamin and caribdotoxin on the inhibitory junction potential in smooth muscle of rat colon., AR.EXT

Abstract

The project has the general objective to study the muscle-sympathetic nerve transmission, using the mouse deferent duct transplanted into the intestinal wall. The organ will be used as a model for denervation and for renervation of the sympathetic nervous system, since at the start of the transplant (first 7 days) there is denervation of the duct, followed by renervation (14 to 180 days). The specific objectives will be focused on the effect of different drugs and neurotransmitters in the post-junctional component (that is, in the smooth muscle), with emphasis on the alterations that should occur in the functional characteristics (and of binding) of alpha-adrenoceptors and on the characteristics of the translocation of calcium and of ionic channels and their blockers, during the processes of nerve degeneration and regeneration The transplanted duct will be studied in an integrated manner, using 5 different methodologies: a) dose-effect curves in the whole organ (contraction induced by alpha-adrenergic agonists in the presence or not of antagonists); b) -"binding” in preparations of cell membrane (for adrenergic receptors and for receptors of calcium channels sensitive to dihydropiridines); c) electrochemical detection (ELCD) of the liberated neurotransmitter (noradrenalin); d) measurement of the electrical alterations in the cell membrane, by sucrose-gap or patch clamp and e) measurement, in isolated cells, of transients of calcium caused by adrenergic drugs. As controls we will use normal ducts, denerved (by surgery or by hypothermia), or of castrated animals. As to the relevance of the project, the information obtained should be useful not only for better understanding of the plasticity of the adrenoreceptors and their interrelation with the translocation of calcium, but also in transplant surgery and in the development of drugs that act on sympathetic neurotransmission, for the treatment of maladies whose etiopathogeny or therapy are related in part to sympathetic neurotransmission, such as hypertension and bronchial asthma. In terms of infrastructure, the team has most of the equipment necessary. In terms of budget, the project is destined mainly to the purchase of consumables, the expansion of some activities and the replacement of deficient or unsuitable equipment, or which has been borrowed from other sectors of the institution. (AU)