Dihydropyridine ligands influence the evoked release of oxytocin and vasopressin dependent on stimulation conditions.
The effects of dihydropyridine ligands on the electrically evoked release of neurohypophysial hormones from isolated, rat neurointermediate lobes were investigated as a function of all combinations of two pulse widths (0.2 and 2 ms) and three stimulation frequencies (6.5, 13 and 30 Hz). The dihydropyridine agonist (S)-(+)-202-791 potentiated concentration dependently the release of both oxytocin and vasopressin at a pulse width of 2 ms and a frequency of 6.5 Hz. This effect of (S)-(+)-202-791 was abolished by the antagonist (-)-nitrendipine and stereospecifically by (R)-(-)-202-791 (only vasopressin). The antagonist (R)-(-)-202-791 alone inhibited the release of oxytocin at 13 Hz and 2 ms. The results presented show that the effects of the dihydropyridine ligands are dependent on the stimulation conditions, and thus demonstrate that the entry of Ca2+ through the dihydropyridine sensitive L-type Ca2+ channel is associated with electrically evoked release of neurohypophysial hormones under certain conditions.
Department of Biological Sciences, Royal Danish School of Pharmacy, Copenhagen.
A
A
Jørgensen
B
B
Fjalland
J D
JD
Christensen
M
M
Treiman
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D008024:Ligands; D009539:Nicotinic Acids / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010069:Oxadiazoles; D010121:Oxytocin / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014667:Vasopressins / Q000378:metabolism*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008024:Ligands; D009539:Nicotinic Acids; D010069:Oxadiazoles; C049834:PN 202-791; D014667:Vasopressins; D010121:Oxytocin; C038806:1,4-dihydropyridine; D009568:Nitrendipine