Sympatho‐adrenal secretion in humans: factors governing catecholamine and storage vesicle peptide co‐release *

Abstract

1. In postganglionic sympathetic neurones and adrenal chromaffin cells, catecholamines are co-stored in vesicles with soluble peptides, including chromogranin A (CgA) and neuropeptide Y (NPY), which are subject to exocytotic co-release with catecholamines. 2. Plasma catecholamine, CgA and NPY responses to stimulators and inhibitors of sympatho-adrenal catecholamine storage and release were measured in humans. Short-term, high-intensity dynamic exercise, prolonged low-intensity dynamic exercise, and assumption of the upright posture, in decreasing order of potency, predominantly stimulated noradrenaline (NA) release from sympathetic nerve endings. Only high-intensity exercise elevated CgA and NPY, which did not peak until 2 min after exercise cessation. Stimulated NA correlated with plasma CgA 2 min after exercise, and with NPY 5 min after exercise. 3. Insulin-evoked hypoglycaemia and caffeine ingestion, in decreasing order of potency, predominantly stimulated adrenaline (AD) release from the adrenal medulla. During insulin hypoglycaemia AD and CgA rose, but NPY was unchanged. Neither NPY nor CgA were altered by caffeine. The rise in CgA after intense adrenal medullary stimulation was greater than its rise after intense sympathetic neuronal stimulation (1.4-versus 1.2-fold, respectively). 4. Infusion of tyramine, which disrupts sympathetic neuronal vesicular NA storage, elevated systolic blood pressure and NA, while NPY and CgA were unchanged. After reserpine, another disruptor of neuronal NA storage, NA transiently rose and then fell; NPY and CgA were unaltered. After the non-exocytotic adrenal medullary secretory stimulus glucagon. AD rose while NA, CgA and NPY did not change. After amantadine, an inhibitor of protein endocytosis, both CgA and fibrinogen rose, while NA and NPY remained unaltered. Neither CgA, NPY, nor catecholamines were altered by the catecholamine uptake and catabolism inhibitors desipramine, cortisol, and pargyline. 5. Human sympathetic nerve contained a far higher ratio of NPY to catecholamines than human adrenal medulla, while adrenal medulla contained far more CgA than sympathetic nerve. 6. It is concluded that peptides are differentially co-stored with catecholamines, with greater abundance of CgA in the adrenal medulla and NPY in sympathetic nerve. Activation of catecholamine release from either the adrenal medulla or sympathetic nerves, therefore, results in quite different changes in plasma concentrations of the catecholamine storage vesicle peptides CgA and NPY. Only profound, intense stimulation of chromaffin cells or sympathetic axons measurably perturbs plasma CgA or NPY concentration; lesser degrees of stimulation perturb plasma catecholamines only. Neither CgA nor NPY are released during non-exocytotic catecholamine secretion.

Effects of caffeine on glucose tolerance: A placebo-controlled study

“…There is a possibility that the glycaemic trend observed in our study is due to caffeine-induced catecholamine release (Robertson et al, 1978;Denaro et al, 1981;Jung et al, 1981;Onrot et al, 1985;Kerr et al, 1993;Nehlig & Debry, 1994;Takiyyuddin et al, 1994;Leblanc et al, 1995). Caffeine is also an adenosine receptor antagonist (Leblanc & Soucy, 1994) and therefore able to inhibit muscle glucose uptake even in the presence of insulin (Vergauwen et al, 1994), and this is another hypothesis to be veri®ed.…”

Activity-Dependent Differential Transmitter Release in Mouse Adrenal Chromaffin Cells

“…A proposed mechanism for this model is provided in Figure 6 and addresses the observation that catecholamine and neuropeptides are differentially released according to sympathetic activity (Takiyyuddin et al, 1990(Takiyyuddin et al, , 1994Watkinson et al, 1990). Under low activity levels, chromaffin cells contribute to the breed and feed state by releasing catecholamine from secretory granules through a restricted fusion pore (Figs.…”

“…Catecholamines and neuropeptides are copackaged in the same granule (Winkler and Westhead, 1980); thus, it was assumed that both types of transmitter are released by a single exocytic mechanism (Viveros et al, 1969). However, this is inconsistent with reports of activity-dependent differential release of catecholamine and neuropeptides from chromaffin cells (Takiyyuddin et al, 1990(Takiyyuddin et al, , 1994Watkinson et al, 1990;Cavadas et al, 2002), clonal PC-12 cells (Wilson et al, 1981), and transmitter levels measured in the circulation (Giampaolo et al, 2002). Thus, the idea that granule fusion represents the final step in the control of transmitter release from chromaffin granules is insufficient to describe the observed behavior.…”

Deletion of the neuropeptide Y (NPY) Y 1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion

“…adrenal gland ͉ tyrosine hydroxylase ͉ Y1 knockout mice N europeptide Y (NPY) is a 36-aa peptide coreleased with norepinephrine (NE) during sympathetic nerve activation (1,2). NPY acts through different G protein-coupled receptors termed Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 (3,4).…”