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PubMed1982

Further characterization of the aggregation and fusion of chromaffin granules by synexin as a model for compound exocytosis.

Synexin was isolated from bovine liver and found to aggregate adrenal chromaffin granules in the same Ca2+-dependent manner as previously described for adrenal synexin. The chromaffin granule aggregating activity of liver synexin was blocked in vitro by the addition of an antibody prepared to the 47,000 molecular weight band extracted from an SDS gel of an adrenal medullary synexin preparation. Chromaffin granules aggregated by synexin fused when exposed to cis-unsaturated fatty acids at concentrations comparable to those released from phospholipids by stimulated secretory cells. The synexin-induced aggregation reaction was blocked by Erythrosin B, a common food coloring, and by the phenothiazine antipsychotic trifluoperazine and promethazine. The aggregation and fusion of chromaffin granules thus appears to be a useful model system for studying synexin from diverse tissues and for testing pharmacologically or toxicologically active substances for effects on secretory systems.

Adrenal Medulla↗
PubMed1983

Use of isolated chromaffin cells to study basic release mechanisms.

An account is given of the authors' work with isolated adrenal chromaffin cells to study the synthesis, storage and release of catecholamines and of a number of neuropeptides endogenous to the adrenal medulla. A review of other studies in the literature with the isolated chromaffin cell system is included. It is seen that the isolated chromaffin cells are a convenient in vitro system well-suited to studies of basic release mechanisms. The isolated adrenal chromaffin cells maintain high levels of catecholamines and opiates and release them by exocytosis. The cells have both nicotinic and muscarinic receptors but only the nicotinic are involved in the agonist-evoked release of catecholamines (EC50 nicotine 5 X 10(-6) M: ACh 5 X 10(-5) M). The cells can synthesize AChE and selectively release the 10S molecular form by a mechanism different from exocytosis. Substance P (SP) modulates the secretion of catecholamines and ATP evoked by ACh or nicotine but not that evoked by K+ or veratridine. SP appears to interact with the nicotinic receptor-ionophore complex to regulate Na+ entry. SP receptors on the chromaffin cells show similar structural requirements to SP receptors in other SP responsive tissues. Binding studies on isolated chromaffin cell membranes with [4-3H-Phe]SP have shown specific binding in the nM range. In addition, at high concentrations of ACh, SP protects against nicotinic receptor desensitization. Since SP is contained in the splanchnic nerve terminals that innervate the medulla, the demonstration of SP action and SP receptors on the chromaffin cells suggests a physiological role for SP in the regulation of secretion from the adrenal medulla. Somatostatin (SS) and a number of SS analogues also inhibit release, but are approximately 15-fold less potent than SP. Leu- and Met-enkephalin, which are co-stored with adrenaline in the bovine adrenal medullary cells produce a non-specific inhibition of the nicotine-evoked release of CA, but enhance the basal release of endogenous catecholamines by a mechanism that is Ca2+-dependent, stereospecific and reversible by naloxone and naltrexone. The implication of these peptide-amine interactions for physiological processes regulating homeostasis in the adrenal are discussed.

Acetylcholinesterase↗
PubMed1988

Molecular mechanisms of exocytosis: the adrenal chromaffin cell as a model system.

1. The release of neurotransmitters, hormones, and enzymes involves exquisitely regulated events which ultimately result in the fusion of the secretory vesicle with the cell's plasma membrane, releasing the vesicle contents into the extracellular space. 2. The biochemical and cellular mechanisms mediating exocytosis have been extensively studied in a model system of primary cultured adrenal chromaffin cells. 3. This paper briefly reviews current understanding, and directions of future studies in exocytosis using this model system.

Adrenal Medulla↗