Responses to human CGRP, ADM, and PAMP in human thymic arteries.
Responses to human CGRP, adrenomedullin (ADM), and proadrenomedullin NH2-terminal 20 peptide (PAMP) were studied in small human thymic arteries. CGRP, ADM, and PAMP produced concentration-dependent vasodilator responses in arteries preconstricted with the thromboxane mimic U-46619. Responses to ADM and PAMP were attenuated, whereas responses to CGRP were not altered by endothelial denudation. Inhibitors of nitric oxide synthase and guanylyl cyclase attenuated responses to ADM and PAMP but not to CGRP. The CGRP1 receptor antagonist CGRP(8-37) attenuated responses to CGRP and ADM but not to PAMP. Responses to CGRP were reduced by SQ-22536 and Rp-cAMPS, inhibitors of adenylyl cyclase and PKA. These data suggest that responses to CGRP and ADM are mediated by CGRP(8-37)-sensitive receptors and that the endothelial ADM receptor induces vasodilation by a nitric oxide-guanylyl cyclase mechanism, whereas a smooth muscle CGRP receptor signals by a cAMP-dependent mechanism. A different endothelial receptor recognizes PAMP and signals by a nitric oxide-dependent mechanism.
Champion
Hunter C
HC
Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Bivalacqua
Trinity J
TJ
Pierce
Robert L
RL
Murphy
William A
WA
Coy
David H
DH
Hyman
Albert L
AL
Kadowitz
Philip J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D053607:Adrenomedullin; D001158:Arteries / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D013950:Thymus Gland / Q000098:blood supply* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D018015:Receptors, Calcitonin Gene-Related Peptide; D013873:Thionucleotides; D053607:Adrenomedullin; C017759:9-(tetrahydro-2-furyl)-adenine; C016957:adenosine-3',5'-cyclic phosphorothioate; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000225:Adenine; D015740:Calcitonin Gene-Related Peptide