RT Journal Article
SR Electronic
T1 Mechanism of Secretion from the Adrenal Medulla IV. The Fate of the Storage Vesicles following Insulin and Reserpine Administration
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 69
OP 82
VO 5
IS 1
A1 O. H. VIVEROS
A1 L. ARQUEROS
A1 R. J. CONNETT
A1 N. KIRSHNER
YR 1969
UL http://molpharm.aspetjournals.org/content/5/1/69.abstract
AB Rabbits were treated with insulin and with reserpine to obtain information on the mechanism of secretion of catecholamines from the adrenal gland and on the fate of the catecholamine storage vesicles following secretion. Three and twenty-four hours after the intravenous injection of insulin (40 units/kg) there were statistically significant decreases in the contents of catecholamine and dopamine β-hydroxylase activity, and in the ability of the storage vesicles to take up 14C-adrenaline. Forty-eight hours after insulin administration there was a significant recovery of the catecholamine content and the ability to take up 14C-adrenaline. At this time the levels of dopamine β-hydroxylase had returned to normal limits. Four days after insulin treatment the dopamine β-hydroxylase levels were significantly greater than normal and the catecholamine content and uptake of 14C-adrenaline were normal. Six days after insulin administration the dopamine β-hydroxylase levels and catecholamine content were significantly greater than the controls and the uptake was normal. Tyrosine hydroxylase levels remained at normal levels for 24 hr after insulin administration. Forty-eight hours after insulin injection the tyrosine hydroxylase levels were significantly greater than normal; at 96 hr they had increased to twice the normal levels and remained there until the end of the experimental period. Phenylethanolamine N-methyltransferase levels and the protein content were not affected by the insulin treatment. Within 15 min after an injection of reserpine (1 mg/kg) the uptake was almost completely blocked, but the catecholamine content did not differ from the controls at that time or at 3 hr after the injection. Maximal depletion of catecholamines was observed 24 hr after reserpine. Thereafter the catecholamine content and 14C-adrenaline uptake increased, and both were within normal limits at 8 days. The content of dopamine β-hydroxylase remained normal for 3 days after reserpine and at 8 days increased to approximately twice the normal levels. Higher doses of reserpine (5 mg/kg) produced an effect which appeared to be a combination of neurogenic stimulation as induced by insulin and the depletion produced by lower doses of reserpine. These data suggest that during neurogenic stimulation the entire soluble content of the storage vesicles, including dopamine β-hydroxylase, is secreted by exocytosis, leaving the vesicle membranes within the medullary cells. The depletion of catecholamines produced by low doses of reserpine (1 mg/kg) is due mainly to inhibition of the uptake mechanism rather than to neurogenic secretion.