Histamine potentiates IP(3)-mediated Ca(2+) release via thapsigargin-sensitive Ca(2+) pumps.
We have studied the histamine-induced potentiation of inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) release in HeLa cells. Intracellular IP(3) levels were increased by IP(3) dialysis with the whole-cell configuration of the patch-clamp technique (cell dialysis of IP(3)). Low concentrations of extracellular histamine (1 microM) accelerated the rate of IP(3)-mediated Ca(2+) release, an effect that required the coincidence of both histamine signalling and the increase in IP(3) levels. Our data suggest that the potentiation effect of histamine cannot be explained simply by agonist-induced increase in IP(3) levels. Disordering microfilaments with cytochalasin D and microtubules with colchicine caused a decrease in the histamine-induced Ca(2+) response. Furthermore, both cytochalasin D and colchicine diminished the rate of IP(3)-mediated Ca(2+) release, while only the former reduced slightly the histamine-induced potentiation effect. Remarkably, rapid inhibition of SERCA pumps with thapsigargin to avoid the depletion of internal Ca(2+) stores diminished the histamine-induced potentiation of IP(3)-mediated Ca(2+) release, without affecting the rate of IP(3)-mediated Ca(2+) release. These data indicate that histamine-induced potentiation of Ca(2+) release in HeLa cells requires active SERCA pumps and suggest that SERCA pumps are an important factor in determining the efficiency of agonist-induced Ca(2+) release.
Departamento de Bioquímica, CINVESTAV-IPN, Apdo Postal 14-740, DF México 07000, Mexico.
Beatriz
B
Aguilar-Maldonado
Leticia
L
Gómez-Viquez
Lucía
L
García
Rosa M
RM
Del Angel
Jose Antonio
JA
Arias-Montaño
Agustín
A
Guerrero-Hernández
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000187:drug effects* / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D015638:Cytochalasin D; D019284:Thapsigargin; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D003078:Colchicine; D002118:Calcium