Calcitonin gene-related peptides modulate the acute inflammatory response induced by interleukin-1 in the mouse.
Interleukin-1 beta (1 and 5 ng) produced an intense migration of neutrophils into a 6-day-old murine air-pouch at 4 h time-point. Endogenous calcitonin gene-related peptide (CGRP) was found to be involved as a mediator of interleukin-1 beta (5 ng)-induced migration, since the CGRP receptor antagonist, CGRP-(8-37), attenuated the cellular response. The polymorphonuclear leukocyte accumulation induced by both doses of interleukin-1 beta was also potentiated by exogenously added CGRP, a response blocked by CGRP-(8-37). Interleukin-1 beta also caused plasma protein extravasation into the pouch as assessed by measuring leakage of 125I-albumin. Whereas plasma protein extravasation was potentiated by CGRP, again an effect abolished by co-administration of CGRP-(8-37), the antagonist had no effect upon the plasma extravasation induced by the cytokine alone. These results suggest that endogenous CGRP is involved in mediating the cellular response but not plasma protein extravasation evoked by interleukin-1 beta and point to CGRP receptor heterogeneity.
Ahluwalia
A
A
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, UK.
Perretti
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M
D000704:Analysis of Variance; D000818:Animals; D001798:Blood Proteins / Q000187:drug effects* / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007375:Interleukin-1 / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity
D001798:Blood Proteins; D007375:Interleukin-1; D010446:Peptide Fragments; D011994:Recombinant Proteins; C058636:calcitonin gene-related peptide (8-37); D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide