Effect of atrial natriuretic peptide and calcium antagonists on platelet-activating factor-induced contraction and intracellular calcium mobilization in rat mesangial cells.
We studied the effect of platelet-activating factor (PAF-acether) on rat mesangial cells (MC) and the intracellular mechanisms for PAF-acether-mediated MC activation. Contraction was measured as changes in planar cell surface area (PCSA), and intracellular free calcium concentration ([Ca2+]i) was measured as changes in the signal of the fluorescent indicator fura-2. PAF-acether induced a time- and dose-dependent reduction in PCSA and a dose-dependent increase in [Ca2+]i. Both phenomena were abolished by preincubation of the cells with the PAF-acether-binding blockers L652,731 and BN 52021. TMB-8, an inhibitor of intracellular calcium mobilization, partially inhibited both the reduction in PCSA and the increase in [Ca2+]i, whereas the Ca2+ entry blocker verapamil completely inhibited the reduction in PCSA but only partially blocked the increase in [Ca2+]i. Atrial natriuretic peptide (ANP) produced a dose-dependent inhibition of PAF-acether-induced cell contraction, but its effect was not statistically related to changes in [Ca2+]i. These results show that PAF-acether-induced MC contraction is associated with transient increases in [Ca2+]i, but the relaxing effects of ANP and verapamil may require additional physiologic interactions that involve mechanisms other than the [Ca2+]i transient.
Olivera
A
A
Fundación Jiménez Diaz-Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Caramelo
C
C
Arriba
G
G
Lamas
S
S
Rodriguez-Puyol
D
D
Schrier
R W
RW
Rodriguez-Barbero
A
A
López-Novoa
J M
JM
D000704:Analysis of Variance; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D016257:Fura-2 / Q000737:chemistry; D005663:Furans / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D046934:Ginkgolides; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004224:Diterpenes; D005663:Furans; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D009320:Atrial Natriuretic Factor; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran; D014700:Verapamil; C045856:ginkgolide B; D002118:Calcium; D016257:Fura-2