Actions of growth-hormone-releasing hormone on rat pituitary cells: intracellular calcium and ionic currents.
Actions of growth-hormone-releasing hormone (GHRH) on single rat anterior pituitary cells were studied using indo-1 fluorescence to monitor changes in intracellular calcium, [Ca2+]i, and perforated-patch recording to measure changes in membrane potential and ionic currents. GHRH elevated [Ca2+]i in non-voltage-clamped cells by a mechanism that was dependent upon extracellular Na+ and Ca2+ and was blocked by the dihydropyridine Ca(2+)-channel blocker, nitrendipine. Resting cells had a fluctuating membrane potential whose a mean value depolarized by 9 mV in response to GHRH. The membrane-permeant cAMP analogue, 8-(4-chlorophenylthio)cAMP, mimicked the action of GHRH on membrane potential. Under voltage clamping, GHRH activated a small inward current (1-5 pA). Two types of response could be distinguished. The type I response had an inward current that was largest at more negative potentials (-90 mV), and the type II response had inward current that was larger at more positive potentials (-40 to -70 mV). Both types of response were reversible and blocked by removal of extracellular Na+. These results suggest that the rise in [Ca2+]i produced by GHRH in non-voltage-clamped cells results from the activation via cAMP of a Na(+)-dependent conductance, which depolarizes the cell and increases the Ca2+ influx through voltage-gated Ca2+ channels.
Naumov
A P
AP
Institute of Cytology of Russian Academy of Sciences, St. Petersburg.
Herrington
J
J
Hille
B
B
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
D015220:Calcium Channels; D007473:Ion Channels; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D013007:Growth Hormone-Releasing Hormone; D012964:Sodium; D000242:Cyclic AMP