Pharmacological characterisation of Ca2+ channels of the L-type in human peripheral blood lymphocytes.
Ca2+ channels of the L-type were characterised in intact human peripheral blood lymphocytes using a radioligand binding technique and the dihydropyridine-type Ca2+ channel antagonist [3H](+)-PN 200-110 (isopropyl-4-(2,1,3-benzoxadiazol-4-yl)1,4-dihydro-5-methoxycarbon yl-2, 6-dimethyl-3-pyridine carboxylate) as a ligand. [3H](+)-PN 200-110 binding to human peripheral blood lymphocytes was time-, temperature-, concentration-dependent and of high affinity. The dissociation constant (Kd) value was 0.4 +/- 0.02 nM and the maximum binding capacity (Bmax) was 33.5 +/- 1.6 fmol/10(6) cells. Pharmacological analysis of [3H](+)-PN 200-110 binding to human peripheral blood lymphocytes was consistent with the labelling of a Ca2+ channel of the L-type. In fact, dihydropyridine derivatives were the most potent competitors of [3H](+)-PN 200-110 binding, whereas phenylalkylamine and benzothiazepine compounds or non-selective Ca2+ channel modulators were weak or ineffective displacers. These findings are the first observation that human peripheral blood lymphocytes express Ca2+ channels of the L-type. The possibility that Ca2+ channel antagonists may interfere with immune system function is discussed.
Ricci
A
A
Dipartimento di Scienze Cardiovascolari e Respiratorie, Università La Sapienza, Rome, Italy.
Bisetti
A
A
Bronzetti
E
E
Felici
L
L
Ferrante
F
F
Veglio
F
F
Amenta
F
F
D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D017275:Isradipine / Q000493:pharmacokinetics; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D012044:Regression Analysis; D013696:Temperature
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017275:Isradipine