Chromaffin cells of the adrenal medulla continue to serve as a powerful tool to explore the field of neurohumoral secretion. In 1981 PI introduced a preparation to study catecholamine (CA) secretion from the isolated perfused adrenal gland of the rat. Using this preparation a number of physiological and pharmacological properties of secretion have been established. Most recently, several new observations have been made which made, which are of potential importance. The observations are as follows: 1) Secretion of CA is induced by nicotine as well as muscarine. Nicotine enhances influx of Ca45, whereas muscarine does not, although muscarine-evoked secretion is dependent on calcium. Nicotine-evoked secretion is desensitized within 20 min but muscarine-evoked is not up to 45 min. - a possibility of differential routes of mobilization of calcium and its utilization in exocytosis. 2) As long as 2 hr of continuous perfusion with 55 mM K-Krebs solution causes a pronounced secretion of CA, with only a modest degree of desensitization. Excess K-evoked secretion is totally dependent on calcium - a possibility of slow inactivation of calcium channels. 3) A marked secretion of CA obtained during perfusion with 55 mM K-Krebs solution is not associated with a reduction in the medullary CA content; however, after blockade of tyrosine hydroxylase there was a significant reduction in CA content - a possibility of reutilization of chromaffin storage vesicles. 4) Secretion of CA evoked by stimulation of splanchnic nerves at higher frequencies is more effectively reduced by cholinergic receptor antagonists than that evoked at lower frequencies - a possibility of another transmitter, in addition to acetylcholine, (ACh), released from splanchnic nerves to evoke secretion of CA. 5) Protein kinase C activator (phorbol esters) potentiate CA secretion and Ca45 uptake initiated by nicotine. Phorbol esters have no effect on muscarine-evoked secretion. cAMP activator (forskolin) potentiates CA secretion evoked by nicotine as well as muscarine - a possibility of intracellular messengers participating at different steps of exocytosis to evoke secretion. Biochemical, physiological and pharmacological experiments have been designed to discern each of the above possibilities in hope of extending our understanding of the secretory mechanism.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL022170-11
Application #
3336736
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
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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