title: 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.
authors.affiliation: Department of Medicine, University of California, San Diego 92161.
authors.forename: M A
authors.initials: MA
authors.lastname: Takiyyuddin
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: T Q
authors.initials: TQ
authors.lastname: Dinh
authors.forename: J H
authors.initials: JH
authors.lastname: Cervenka
authors.forename: S D
authors.initials: SD
authors.lastname: Braun
authors.forename: R J
authors.initials: RJ
authors.lastname: Parmer
authors.forename: B
authors.initials: B
authors.lastname: Kennedy
authors.forename: D T
authors.initials: DT
authors.lastname: O'Connor
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000547:Amantadine / Q000494:pharmacology; D000704:Analysis of Variance; D002110:Caffeine / Q000494:pharmacology; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D015444:Exercise; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000097:blood / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011187:Posture; D014439:Tyramine / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D009478:Neuropeptide Y; D002110:Caffeine; D000547:Amantadine; D009638:Norepinephrine; D014439:Tyramine