Canadian journal of physiology and pharmacology
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Can. J. Physiol. Pharmacol. · Jun 1997
Bradykinin activates R-, T-, and L-type Ca2+ channels and induces a sustained increase of nuclear Ca2+ in aortic vascular smooth muscle cells.
The mechanism(s) fo Ca2+ entry stimulated by bradykinin (BK) and the receptor subtype responsible for this effect were examined in human and rabbit aortic vascular smooth muscle cells (VSMCs). Using the whole-cell voltage clamp technique, BK (10(-6)M) significantly (p < 0.05) increased both T- and L-type Ca2+ currents (ICa) in rabbit aortic VSMCs. Using the fura-2 total intracellular Ca2+ ([Ca]i) measurement technique, BK (10(-6) M) induced a transient increase of [Ca]i followed by a sustained component. ⋯ These results strongly suggest that B1 and probably B2 receptors are functional in human and rabbit aortic VSMCs. BK-induced transient increase of [Ca]i is mainly due to the stimulation of T- and L-type Ica as well as to Ca2+ release from caffeine- and ryanodine-sensitive Ca2+ pools. The sustained component induced by the hormone or the B1 agonist is mainly nuclear and is due to the stimulation of Ca2+ influx through the R-type Ca2+ channels that are present at the sarcolemma and the nuclear membranes.
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Can. J. Physiol. Pharmacol. · Jun 1997
Partial agonists and full antagonists at the human and murine bradykinin B1 receptors.
We developed a functional assay to evaluate the activity of kinin peptides at the human and mouse bradykinin (BK) B1 receptors. The photoprotein aequorin expressed in 293-AEQ17 cells was used to measure calcium mobilization due to activation of the human or mouse B1 receptors by kinin peptides. The B1 agonists des-Arg9-BK and des-Arg10-kallidin activated the human receptor (EC50 = 112 and 5 nM, respectively), whereas the B1 peptide antagonists des-Arg9,Leu8-BK and des-Arg10,Leu9-kallidin showed no activation. ⋯ Thirty-nine and 44% agonism of the mouse receptor was observed with des-Arg9,Leu8-BK (EC50 = 56 nM) and des-Arg10,Leu9-kallidin (EC50 = 177 nM). Two recently described kinin analogues, [Lys-Lys0,Hyp3,Igl5,D-Igl7,Oic8,des-Arg9]B K and [D-Arg0,Hyp3,Igl5,D-Igl7, Oic8,des-Arg9]BK (B9858 and des-Arg9-B9430), failed to agonize the mouse receptor. These peptides were potent antagonists of des-Arg10-kallidin- and des-Arg9-BK-induced bioluminescence at the cloned human and mouse B1 receptors.