Effects of bromocriptine on prolactin release, electrical membrane properties and transmembrane Ca2+ fluxes in cultured rat pituitary adenoma cells.
The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical membrane properties and transmembrane Ca2+ fluxes have been studied in a clonal strain of rat pituitary adenoma cells (GH3). These cells generate Ca2+ dependent action potentials, and produce and secrete spontaneously both Prl and growth hormone. Prl release stimulated by thyroliberin (TRH) and elevated extracellular K+ concentration was completely blocked by bromocriptine, whereas the basal release was only moderately affected. The TRH and K+ evoked Prl release were half maximally inhibited by bromocriptine at 5-10 and 10-50 microM, respectively. The normal biphasic membrane response to TRH and the depolarizing effect of elevated K+ concentration were not altered by bromocriptine, whereas the Ca2+- spikes in Na+-free solution were suppressed by the drug. We therefore suggest that bromocriptine blocks the voltage sensitive Ca2+-channels of GH3 cell. In agreement with this notion, bromocriptine also suppressed the basal and TRH induced 45Ca2+ efflux from preloaded cells. We conclude that the inhibitory effect of bromocriptine on the voltage dependent Ca2+- channels is an important mechanism responsible for suppression of Prl release.
Johansen
P W
PW
Sand
O
O
Iversen
J G
JG
Haug
E
E
Gautvik
K M
KM
D000200:Action Potentials / Q000187:drug effects*; D000236:Adenoma / Q000503:physiopathology*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D010911:Pituitary Neoplasms / Q000503:physiopathology*; D011189:Potassium Chloride / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D001971:Bromocriptine; D013973:Thyrotropin-Releasing Hormone; D011189:Potassium Chloride; D011388:Prolactin; D002118:Calcium