The actions of caffeine and 2,3-butanedione monoxime on calcium transients in human vascular smooth muscle.
Ca2+ mobilization by membrane depolarization or histamine application, was measured in isolated human uterine artery smooth muscle cells. Nifedipine, a Ca2+ channel blocker, was found to inhibit the depolarization-induced increase in [Ca2+]i but not the histamine-induced increase. This suggests the presence of functional voltage-dependent Ca2+ channels and agonist-induced mobilization of Ca2+ via a different mechanism. Caffeine inhibited both the depolarization- and histamine-induced increases in intracellular calcium. The mechanisms of inhibition do not involve cAMP and point to a complex action of caffeine at multiple sites. The dephosphorylating agent 2,3-butanedione monoxime (BDM) was found to block voltage-dependent Ca2+ changes but not agonist-induced changes suggesting a role for phosphorylation in the regulation of the Ca2+ channels in these cells.
Department of Physiological Sciences, Medical School, The University, Newcastle upon Tyne.
H
H
Otun
J I
JI
Gillespie
J R
JR
Greenwell
W
W
Dunlop
D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism
D015220:Calcium Channels; C004717:diacetylmonoxime; D002110:Caffeine; D006632:Histamine; D012964:Sodium; D009543:Nifedipine; D003931:Diacetyl; D011188:Potassium; D002118:Calcium