Bradykinin-evoked Ca2+ mobilization in Madin Darby canine kidney cells

• Published in: European journal of pharmacology 1998-08, Vol.355 (2-3), p.219-233
• Main Authors: JAN, C.-R, HO, C.-M, WU, S.-N, TSENG, C.-J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bradykinin - pharmacology; Calcium - metabolism; Cell Line; Cyclic GMP - physiology; Dogs; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Kidney - drug effects; Kidney - metabolism; Receptor, Bradykinin B2; Receptors, Bradykinin - agonists; Receptors, Bradykinin - physiology; Type C Phospholipases - metabolism; Vertebrates: urinary system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00481-6

We studied the mechanisms underlying the bradykinin-evoked changes in intracellular calcium concentration ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells. Bradykinin evoked a [Ca2+]i transient in a dose-dependent manner, measured by fura-2 fluorimetry and digital video imaging. The transient consisted of a rise and a decay and [Ca2+]i returned to baseline without oscillations. External Ca2+ influx occurred, as demonstrated by Mn2+ quench and external Ca2+ removal measurements. Bradykinin acted by stimulating bradykinin B2 receptors as evidenced by blockade by D-arginyl-L-arginlyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl -3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3-isoquinolineca rbonyl-L-(2alpha,3beta,7alphabeta)-octahydro-1 H-indole-2-carbonyl-L-arginine (HOE 140) but not by D-arginyl-L-arginlyl-L-prolyl-trans-4-hydroxy-L-proylglycyl- 3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3-isoquinolinecar bonyl-L-(2alpha,3beta,7alphabeta)-octahydro-1 H-indole-2-carbonyl ([Des-Arg]HOE 140). The [Ca2+]i signal was abolished by 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1 H-pyrrole-2,5-dione (U73122) and partially inhibited by neomycin, implying mediation by phospholipase C. The transient was initiated by a release of Ca2+ from internal stores since it was abolished by pretreatment with thapsigargin or cyclopiazonic acid. The mobilization of the internal Ca2+ store subsequently triggered a 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1 H-imidazole hydrochloride (SKF 96365)-insensitive Ca2+ entry. Pretreatment with carbonylcyanide m-chlorophynylhydrozone and gly-phe-beta-naphthylamide did not alter the transient, thus excluding the participation of mitochondria and lysosomes. Efflux via Ca2+ pumps contributed to the decay of the transient. Efflux via Na+/Ca2+ exchange or sequestration by mitochondria and lysosomes was insignificant. The transient was blunted by the protein kinase C activator phorbol 12-myristate 13-acetate, and was enhanced by the protein kinase C inhibitors sphingosine and chelerythrine, the protein kinase A inhibitor 2,5-di-(t-butyl)-1,4-hydroquinone, N-[2-(p-bromocinnamylamino)ethyl]5-isoquinolinesulfonamide (H-89), the agent 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), and agents that elevated levels of 3',5'-cyclic guanosine monophosphate. The transient did not heterologously desensitize with that evoked by ATP, ADP or UTP.