Lidocaine and procaine inhibit the increase in cytosol Ca2+ induced by thyrotropin-releasing hormone or K+ depolarization in GH4C1 cells.
Lidocaine at greater than or equal to 1 mM and procaine at greater than or equal to 2.5 mM exerted dose-dependent inhibition of the increment in [Ca2+]i induced by 100 nM thyrotropin-releasing hormone (TRH) or 30 mM K+ in GH4C1 cells. The rise in [Ca2+]i induced by K+ was more sensitive to this inhibition than that induced by TRH. Lidocaine was more potent than procaine in inhibiting the [Ca2+]i increment induced by secretagogues. Maximal lidocaine inhibition of the TRH-induced [Ca2+]i increment occurred within 15-20 min and a normal response to secretagogues returned within 20 min after removal of lidocaine from the incubation medium. Our data suggest that in GH4C1 cells local anesthetics depress secretagogue-induced intracellular Ca2+ mobilization, depolarization of the cell membrane, and the opening of voltage-dependent Ca2+ channels. This may explain the depression of secretagogue-stimulated hormone secretion induced by these agents.
Wang
X B
XB
Department of Medicine, Oregon Health Sciences University, Portland 97201.
Sato
N
N
Greer
M A
MA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008012:Lidocaine / Q000494:pharmacology*; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013997:Time Factors
D015220:Calcium Channels; D011343:Procaine; D013973:Thyrotropin-Releasing Hormone; D008012:Lidocaine; D011188:Potassium; D002118:Calcium