Mechanism of CGRP-induced vasodilation in the rat isolated perfused kidney.
We investigated the intracellular mechanisms involved in calcitonin gene-related peptide (CGRP)-induced vasodilation in rat isolated perfused kidney. CGRP-1 receptor antagonist, CGRP-8-37, abolished the responses. Endothelial denudation by Triton X-100 or nitric oxide (NO) synthase inhibition by NG-nitro-L-arginine attenuated the maximum dilation by about 63 and 55%, respectively. Protein kinase A inhibitor, KT-5720, caused an about 72% inhibition in CGRP-induced maximum dilation. Soluble guanylate cyclase inhibitor, ODQ, and ATP-sensitive potassium channel blocker, glibenclamide, inhibited the CGRP-induced maximum responses by 75 and 55%, respectively. Cyclooxygenase inhibitor, indomethacin, had no effect. Our data suggest that CGRP-1 receptors, endothelium, NO synthase, protein kinase A, soluble guanylate cyclase, and ATP-sensitive potassium channels, but not the cyclooxygenase pathway, may play a role in CGRP-induced vasodilation in rat isolated perfused kidney.
Ay
Ilknur
I
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Tuncer
Meral
M
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002227:Carbazoles / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006162:Guanylate Cyclase / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D019335:Nitroarginine / Q000494:pharmacology; D017830:Octoxynol / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002227:Carbazoles; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D010446:Peptide Fragments; D015221:Potassium Channels; D011758:Pyrroles; C058636:calcitonin gene-related peptide (8-37); D019335:Nitroarginine; C057416:KT 5720; D017830:Octoxynol; D017868:Cyclic AMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin