The role of sodium in mediating adrenocorticotropin secretion by perifused rat anterior pituitary cells.
We studied the role of sodium ions in mediating basal and stimulated ACTH release from perifused rat anterior pituitary cells by exposing the cells to the sodium channel opener veratridine or the Na+/K(+)-adenosine triphosphatase inhibitor ouabain to increase the intracellular Na+ concentration or, conversely, by omitting Na+ from the perifusion medium or blocking Na+ entry into the cell with tetrodotoxin, a voltage-dependent sodium channel blocker, to decrease the intracellular Na+ concentration. Neither tetrodotoxin nor Na(+)-free medium had a significant effect on 100 nM arginine vasopressin (AVP) or 10 nM ovine corticotropin-releasing hormone (CRH)-induced ACTH secretion. Veratridine increased basal ACTH secretion by 122% (41.3 +/- 2.9 vs. 18.6 +/- 0.4 pg/min; P < 0.001), the initial spike phase of the response to AVP by 65% (0.28 +/- 0.01 vs. 0.17 +/- 0.03 ng/3 min; P < 0.005), the subsequent sustained phase to AVP by 129% (0.16 +/- 0.01 vs. 0.07 +/- 0.01 ng/7 min; P < 0.005), and the total response to CRH by 70% (0.39 +/- 0.01 vs. 0.23 +/- 0.04 ng/10 min; P < 0.05). Ouabain increased basal ACTH secretion by 39% (45.7 +/- 2.8 vs. 32.9 +/- 2.1 pg/min; P < 0.05), the initial spike phase of the response to AVP by 88% (0.32 +/- 0.02 vs. 0.17 +/- 0.01 ng/3 min; P < 0.005), the sustained phase response to AVP by 67% (0.10 +/- 0.01 vs. 0.06 +/- 0.01 ng/7 min; P < 0.05), and the total integrated response to CRH by 49% (0.88 +/- 0.09 vs. 0.59 +/- 0.03 ng/10 min; P < 0.05). However, the effects of both veratridine and ouabain on basal ACTH secretion were significantly attenuated in Ca(2+)-free EGTA-containing medium, suggesting that this effect was indirect, due to membrane depolarization and consequent influx of extracellular Ca2+. Dexamethasone (100 nM) had no effect on the ACTH response to either veratridine or ouabain. We conclude that changes in the intracellular Na+ concentration and sodium channel activity are not directly involved in AVP- or CRH-induced ACTH secretion.
Halili-Manabat
C
C
Department of Medicine, Hamamatsu University School of Medicine, Japan.
Oki
Y
Y
Iino
K
K
Iwabuchi
M
M
Morita
H
H
Yoshimi
T
T
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D015222:Sodium Channels; D001127:Arginine Vasopressin; D013779:Tetrodotoxin; D010042:Ouabain; D014701:Veratridine; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium