Chromogranin A. Storage and release in hypertension.

Abstract

The chromogranins/secretogranins are a family of acidic, soluble proteins with widespread neuroendocrine distribution in secretory vesicles. Although the precise function of the chromogranins remains elusive, knowledge of their structure, distribution, and potential intracellular and extracellular roles, especially that of chromogranin A, has greatly expanded during recent years. Chromogranin A is coreleased with catecholamines by exocytosis from vesicles in the adrenal medulla and sympathetic nerve endings. Thus, measurement of its circulating concentration by radioimmunoassay may be a useful probe of exocytotic sympathoadrenal activity in humans, under both physiological and pathological conditions. Here, we explore the storage, structure, and function of chromogranin A, and parameters that influence its circulating levels. We have also measured plasma chromogranin A concentrations in different groups of patients with hypertension, including those with pheochromocytoma. (Hypertension 1990;15:237-246)

Chromogranin A: a surprising link between granule biogenesis and hypertension

“…This is consistent with observations that hypertensive patients and subjects with normal blood pressure but with genetic risk of hypertension have decreased catestatin levels compared to those of normotensive controls (16). Interestingly, while catestatin levels were low in these patients, plasma CHGA levels and catecholamine excretion both increased (5,17). One possible explanation for this result is that there is a processing defect of CHGA in these hypertensive patients.…”

“…CHGA and its processed products have been shown to be involved in the biogenesis of densecore secretory granules (2), to have a role in immunity against microbes (3), and to function as potential markers for several types of tumors (4). They have also been implicated in neurodegenerative disorders and cardiovascular diseases such as hypertension (4)(5)(6). However, these proposed functions of CHGA have not previously been verified in vivo.…”

Stimulus coupling to transcription versus secretion in pheochromocytoma cells. Convergent and divergent signal transduction pathways and the crucial roles for route of cytosolic calcium entry and protein kinase C.

“…When chromaffin cells and sympathetic axons release by exocytosis their complement of cosecreted catecholamines and peptides (2), mechanisms are activated to replenish secretory vesicles with the just-secreted components. The rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (3,4), is transcriptionally activated by the physiologic nicotinic cholinergic signal to chromaffin cell exocytosis.…”

“…Chromogranin A is the quantitatively major protein stored and released with catecholamines (2). It is a prohormone, giving rise by proteolytic cleavage to several biologically active peptides (9).…”

Common Genetic Variants in the Chromogranin A Promoter Are Associated with Renal Injury in IGA Nephropathy Patients with Malignant Hypertension

“…[3] CHGA is required for the formation of catecholamine secretory vesicles in chromaffin cells, and its expression may be sufficient to induce a regulated secretory system even in non-secretory cells. [4] CHGA is also a pro-hormone that gives rise to biologically active peptides that inhibit catecholamine release.…”