Dissimilar mechanisms of Ca(2+) response to bradykinin in different types of juxtamedullary glomerular arterioles.
Bradykinin (BK)-induced changes in intracellular calcium level ([Ca(2+)](i)) were studied on fura 2-loaded afferent (AA) and efferent glomerular arterioles (EA) microdissected from juxtamedullary renal cortex. A distinction was made between thin and muscular EA. In AA and both types of EA, BK increased [Ca(2+)](i) through activation of B(2) receptors located only on the endothelium. The responses were not affected by nifedipine (10(-6) M) and were smaller in a Ca(2+)-free medium, providing evidence that BK opens voltage-independent Ca(2+) channels and mobilizes intracellular Ca(2+). Thin EA differed from AA and muscular EA by a lower sensitivity to BK (EC(50) = 6.95 +/- 3.81 vs. 0.21 +/- 0.08 and 0.18 +/- 0.13 nM, respectively; P < 0.05), a higher maximal response (89 +/- 5 vs. 57 +/- 5 and 44 +/- 7 nM; P < 0.001), and a spontaneous return to basal Ca(2+) level, even in the presence of BK. Genistein (10(-4) M) and herbimycin A (25 x 10(-6) M), specific inhibitors of tyrosine kinases, inhibited the [Ca(2+)](i) responses exclusively in AA. Genistein reduced the peak and plateau phases of responses by 69 +/- 9 and 82 +/- 6%, respectively, in a medium with Ca(2+) and the peak by 48 +/- 9% in a Ca(2+)-free medium. Similar reductions were observed with herbimycin A. These results show that dissimilar signal transduction pathways are involved in BK effects on juxtamedullary arterioles and that a tyrosine kinase activity could participate in the regulation of BK effect on AA but not on EA.
Praddaude
F
F
Physiology Laboratory, School of Medicine, 31062 Toulouse Cedex 4, France.
Marchetti
J
J
Alhenc-Gelas
F
F
Ader
J
J
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000378:metabolism
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018002:Receptors, Bradykinin; D011505:Protein-Tyrosine Kinases; D009543:Nifedipine; D001920:Bradykinin; D002118:Calcium