Thyrotropin-releasing hormone activates Ca2+ efflux. Evidence suggesting that a plasma membrane Ca2+ pump is an effector for a G-protein-coupled Ca(2+)-mobilizing receptor.
These studies characterize the mechanisms involved in terminating the initial Ca2+ transient stimulated by thyrotropin-releasing hormone (TRH). When TRH was added to GH3 pituitary cells that had been treated with thapsigargin to block any agonist-stimulated increase in [Ca2+]i, TRH caused a decrease in [Ca2+]i. The Ca2+ clearing response was seen in pituitary GH3 cells and in nonexcitable HEK 293 cells transfected with TRH receptor cDNA, was evident at basal or elevated [Ca2+]i, and was mediated by the TRH receptor. The Ca2+ clearing response to TRH was not prevented by thapsigargin, Ca2+ ionophores, nimodipine, or replacement of extracellular Na+ but was inhibited by La3+. La3+ also increased the duration of the TRH-evoked [Ca2+]i transient. TRH-stimulated Ca2+ extrusion was directly demonstrated using extracellular fluo-3 free acid. TRH produced a 5-20-fold increase in Ca2+ efflux that was independent of extracellular Na+ and inhibited by vanadate. TRH stimulation of Ca2+ efflux was not reproduced by phorbol esters or inhibited by down-regulation of protein kinase C or staurosporine. The results suggest that agonist-activated Ca2+ efflux may be a universal component of an agonist-activated Ca2+ response and further suggest that a plasma membrane Ca2+ pump may be an effector for G-protein-coupled receptors linked to Ca2+ mobilization.
Nelson
E J
EJ
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, New York 14642.
Hinkle
P M
PM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D017136:Ion Transport; D051381:Rats; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D019204:GTP-Binding Proteins; D000252:Calcium-Transporting ATPases; D002118:Calcium