Involvement of CGRP in the inhibitory effect of rutaecarpine on vasoconstriction induced by anaphylaxis in guinea pig.
Previous investigations have indicated that calcitonin gene-related peptide (CGRP), a principal transmitter in capsaicin-sensitive sensory nerves, could alleviate cardiac anaphylaxis injury. Rutaecarpine relaxes vascular smooth by stimulation of CGRP release via activation of vanilloid receptor subtype 1 (VR1). In the present study, we examined the role of capsaicin-sensitive sensory nerves in anaphylactic vessels and the effect of rutaecarpine on antigen-challenged constriction in the guinea pig isolated thoracic aorta. The aortas were challenged with 0.01 mg/ml bovine serum albumin, and the tension of aorta rings was continuously monitored. The amount of CGRP released from thoracic aortas was determined in the absence or presence of rutaecarpine. Antigen challenge caused a vasoconstrictor response concomitantly with an increase in the release of CGRP from the isolated thoracic aorta, and the vasoconstrictor responses were potentiated by CGRP8-37 (10 microM) or capsaicin (1 microM). Pretreatment with diphenhydramine (1 microM) markedly decreased antigen-challenged vasoconstriction. Acute application of capsaicin (0.03 or 0.1 microM) significantly inhibited vasoconstrictor responses. Pretreatment with rutaecarpine (10 or 30 microM) significantly increased CGRP release concomitantly with decrease in antigen-challenged vasoconstriction, which was abolished by CGRP8-37 (10 microM) or capsazepine (10 microM). The present results suggest that an increase in the release of CGRP during vascular anaphylaxis may be a beneficial compensatory response, and that rutaecarpine inhibits antigen-challenged vasoconstriction, which is related to stimulation of endogenous CGRP release via activation of VR1.
Yu
Jing
J
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No. 90, Xiang-Ya Road, Changsha, Hunan 410078, China.
Tan
Gui-Shan
GS
Deng
Pan-Yue
PY
Xu
Kang-Ping
KP
Hu
Chang-Ping
CP
Li
Yuan-Jian
YJ
D000470:Alkaloids / Q000494:pharmacology*; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D000941:Antigens / Q000737:chemistry; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D026121:Indole Alkaloids; D008297:Male; D011799:Quinazolines; D011955:Receptors, Drug / Q000378:metabolism; D050916:TRPV Cation Channels; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D052999:Quinazolinones
D000470:Alkaloids; D000941:Antigens; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D004155:Diphenhydramine; D026121:Indole Alkaloids; D011799:Quinazolines; D011955:Receptors, Drug; D050916:TRPV Cation Channels; D014665:Vasodilator Agents; C494484:TRPV1 receptor; C028632:rutecarpine; D052999:Quinazolinones; C071423:capsazepine