Activation and inactivation of oxytocin and vasopressin release from isolated nerve endings (neurosecretosomes) of the rat neurohypophysis.
Neurosecretory terminals (neurosecretosomes, NSS) were isolated from rat neurohypophyses. High [K+]o or veratridine stimulated secretion of vasopressin and oxytocin by up to approximately 100-fold. Stimulated secretion was dependent on calcium and temperature, and could be elicited from NSS maintained in culture for 4 days. After overnight culture of the NSS, secretion was still inhibited by calcium channel blockers (cobalt, dihydropyridines, omega-conotoxin, D 600) and kappa opiates (dynorphin and U50488). Ionomycin evoked dose- and calcium-dependent hormone release, with a Hill coefficient for calcium of 1.74. High [K+]o enhanced the 5 microM ionomycin-induced secretion, apparently through calcium entry rather than depolarization, as the increase in secretion was abolished by 100 microM D 600. During prolonged depolarization the hormone secretion peaked within 2 min, then declined to near basal levels. Depolarization for 25 min without calcium neither activated secretion nor prevented subsequent secretion on readdition of calcium, suggesting that the decline in secretion was not due to membrane depolarization. Indeed, the rates of decline in secretion were similar for different levels of depolarization (0.070 +/- 0.003 and 0.081 +/- 0.003 min-1 for 25 and 45 mM [K+]o, respectively). Four minutes after the onset of continuous depolarization (45 mM [K+]o) in the presence of calcium, the declining secretion was still dependent on voltage-activated calcium influx through channels sensitive to D 600 and nitrendipine. The results presented here suggest that the decline in secretion during prolonged depolarizing stimuli may be due to exhaustion, inactivation, or desensitization of a calcium-triggered event.
Payza
K
K
Unit on Neuronal Secretory Systems, NICHD, National Institutes of Health, Bethesda, Maryland 20892.
Russell
J T
JT
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010121:Oxytocin / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014667:Vasopressins; D005711:Gallopamil; D010121:Oxytocin; D015759:Ionomycin; D014701:Veratridine; D002118:Calcium