The general objective is to elucidate the mechanisms by which local factors influence transmission at adrenergic synapses. Specific investigations will be concerned with (1) characteristics of the inhibitory presynaptic adrenergic and cholinergic receptors on adrenergic nerve terminals, and the mechanisms by which stimulation of these receptors modulates release of the neurotransmitter, norepinephrine; (2) the influx of calcium ions into the adrenergic nerve terminals associated with nerve stimulation and the subsequent release of norepinephrine, and the influence on this influx of frequency of stimulation and of drugs and agents which inhibit or potentiate norepinephrine release; (3) role of intracellular calcium in norepinephrine release; (4) mechanism of action of neuronal blocking agents such as guanethidine and bretylium; (5) the physiological reuse for exocytosis of catecholamine storage vesicles in adrenergic nerve terminals and in the adrenal medulla after they have undergone initial exocytosis. Most experiments will be carried out on perfused organs and isolated organs and tissues, some with sympathetic nerves attached and available for stimulation. Physiological, pharmacological, and biochemical approaches will be employed. Use will be made of radioactive-labeled compounds when appropriate.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Neurological Sciences Subcommittee 1 (NLS)
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Suny Downstate Medical Center
Schools of Medicine
United States
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Wakade, A R; Wakade, T D; Poosch, M et al. (1996) Noradrenaline transport and transporter mRNA of rat chromaffin cells are controlled by dexamethasone and nerve growth factor. J Physiol 494 ( Pt 1):67-75
Lopez, M G; Shukla, R; Garcia, A G et al. (1992) A dihydropyridine-resistant component in the rat adrenal secretory response to splanchnic nerve stimulation. J Neurochem 58:2139-44
Carmichael, S W; Brooks, J C; Malhotra, R K et al. (1989) Ultrastructural demonstration of exocytosis in the intact rat adrenal medulla. J Electron Microsc Tech 12:316-22
Malhotra, R K; Wakade, T D; Wakade, A R (1988) Comparison of secretion of catecholamines from the rat adrenal medulla during continuous exposure to nicotine, muscarine or excess K. Neuroscience 26:313-20
Malhotra, R K; Bhave, S V; Wakade, T D et al. (1988) Protein kinase C of sympathetic neuronal membrane is activated by phorbol ester--correlation between transmitter release, 45Ca2+ uptake, and the enzyme activity. J Neurochem 51:967-74
Wakade, A R; Wakade, T D; Malhotra, R K et al. (1988) Excess K+ and phorbol ester activate protein kinase C and support the survival of chick sympathetic neurons in culture. J Neurochem 51:975-83
Malhotra, R K; Wakade, T D; Wakade, A R (1988) Vasoactive intestinal polypeptide and muscarine mobilize intracellular Ca2+ through breakdown of phosphoinositides to induce catecholamine secretion. Role of IP3 in exocytosis. J Biol Chem 263:2123-6
Malhotra, R K; Wakade, A R (1987) Vasoactive intestinal polypeptide stimulates the secretion of catecholamines from the rat adrenal gland. J Physiol 388:285-94
Malhotra, R K; Wakade, A R (1987) Non-cholinergic component of rat splanchnic nerves predominates at low neuronal activity and is eliminated by naloxone. J Physiol 383:639-52
Harish, O E; Kao, L S; Raffaniello, R et al. (1987) Calcium dependence of muscarinic receptor-mediated catecholamine secretion from the perfused rat adrenal medulla. J Neurochem 48:1730-5

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