Histamine stimulated synaptosomal Ca2+ uptake through activation of calcium channels.
Histamine stimulated Ca2+ uptake in synaptosomes was completely inhibited by the slow Ca2+ channel antagonists verapamil, cinnarizine and flunarizine, and slightly inhibited by nifedipine and diltiazem. Ca2+ uptake in synaptosomes depolarized or predepolarized with varying K+ concentrations was increased by histamine, in both conditions, until 30mM K+. At higher K+ concentrations histamine was not able to alter K+ effects in either conditions. 30mM K+ stimulated uptake of Ca2+ in the absence or presence of histamine was not inhibited by verapamil and diltiazem. However nifedipine slightly inhibited K+ and K+ +histamine effects. 3-Isobutyl-1-methyl-xanthine and dibutyryl cyclicAMP potentiated (10%) the uptake of Ca2+ in synaptosomes induced by histamine. Dibutyryl cyclicAMP alone however decreased the basal Ca2+ uptake in a concentration-dependent manner. Verapamil, but not diltiazem, antagonized the effects elicited by 3-isobutyl-1-methyl-xanthine and dibutyryl cyclicAMP in the presence of histamine. The data suggest that the increase in synaptosomal Ca2+ uptake induced by histamine is mediated by the activation of the voltage sensitive calcium channels, and possibly a cyclicAMP-dependent protein kinase phosphorylation can modulate the opening of Ca2+ channels.
Rodriguez
R
R
Departamento de Bioquímica y Biología Molecular Facultad de Medicina, Universidad Autónoma de Barcelona, Spain.
Toledo
A
A
Brandner
R
R
Sabrià
J
J
Rodriguez
J
J
Blanco
I
I
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002936:Cinnarizine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D002936:Cinnarizine; D003994:Bucladesine; D006632:Histamine; D014700:Verapamil; D000242:Cyclic AMP; D004110:Diltiazem; D009543:Nifedipine; D005444:Flunarizine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine