Effect of atrial natriuretic peptide and calcium antagonists on platelet-activating factor-induced contraction and intracellular calcium mobilization in rat mesangial cells

• Published in: Journal of cardiovascular pharmacology Vol. 24; no. 3; p. 388
• Main Authors: Olivera, A, Caramelo, C, Arriba, G, Lamas, S, Rodriguez-Puyol, D, Schrier, R W, Rodriguez-Barbero, A, López-Novoa, J M
• Format: Journal Article
• Language: English
• Published: United States 01.09.1994
• Subjects: Analysis of Variance; Animals; Atrial Natriuretic Factor - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cells, Cultured; Diterpenes; Dose-Response Relationship, Drug; Fura-2 - chemistry; Furans - pharmacology; Gallic Acid - analogs & derivatives; Gallic Acid - pharmacology; Ginkgolides; Glomerular Mesangium - cytology; Glomerular Mesangium - drug effects; Glomerular Mesangium - metabolism; Hydrogen-Ion Concentration; Lactones - pharmacology; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Platelet Activating Factor - antagonists & inhibitors; Platelet Activating Factor - pharmacology; Rats; Rats, Wistar; Spectrometry, Fluorescence; Verapamil - pharmacology
• ISSN: 0160-2446
• DOI: 10.1097/00005344-199409000-00006

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.