Growth hormone releasing factor depolarizes rat pituitary cells in Na+-dependent mechanism.
Human growth hormone releasing factor (hGRF) is a specific stimulator of growth hormone (GH) secretion from somatotrophs both in vivo and in vitro. In this secretory process of GH adenosine 3',5'-cyclic monophosphate (cAMP) is thought to function as an intracellular mediator. The influx of Ca2+ from the extracellular space is indispensable for hGRF-induced GH secretion, which probably occurs through voltage-sensitive Ca2+ channels. We recently demonstrated that the extracellular Na+ is also essential for hGRF-induced GH secretion and proposed the possibility that hGRF depolarizes somatotrophs by increasing membrane Na+ conductance via cAMP, thereby activating voltage-sensitive Ca2+ channels, which in turn facilitate GH secretion. To directly demonstrate this possibility, we measured changes in both the membrane potentials and the intracellular Ca2+ concentration with fluorescent dyes bis-oxonol and fura 2 respectively and found that: (1) hGRF depolarized rat somatotrophs, (2) this hGRF-induced depolarization was greatly suppressed by replacing extracellular Na+ with mannitol or tris(hydroxymethyl)aminomethane (Tris+), but not by removing Ca2+ from the extracellular solution, and (3) hGRF augmented the intracellular Ca2+ concentration, which depended on both extracellular Ca2+ and Na+.
Kato
M
M
Department of Physiology, Gunma University, Maebashi, Japan.
Suzuki
M
M
D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012964:Sodium / Q000502:physiology*
D005456:Fluorescent Dyes; D013007:Growth Hormone-Releasing Hormone; D012964:Sodium; D002118:Calcium