The hypothermic and antinociceptive effects of intrathecal injection of CGRP (8-37) in mice.
Calcitonin gene-related peptide (CGRP) and the selective antagonist properties of the peptide fragment of CGRP [CGRP (8-37)] have been the subjects of numerous investigations. These data represent the first demonstration of the hypothermic and antinociceptive effects of CGRP (8-37). Intrathecal injection of CGRP (8-37) in mice produced hypothermia which differed from that produced by CGRP in time course, duration of action and potency. CGRP and CGRP (8-37) did not alter blood flow. Thus, a direct vasodilatory action was not responsible for the acute hypothermic effects of the drugs. The combination of CGRP and CGRP (8-37) resulted in a decrease in body temperature which was no greater than that of either drug alone. We failed to observe any significant antinociceptive effect in the tail-flick assay after i.t. injection of CGRP (8-37), but dose-dependent antinociception was produced by CGRP (8-37) in the p-phenylquinone (PPQ) assay, with an ED50 value of 6.0 micrograms. However, CGRP (8-37) failed to block or enhance the antinociception produced by CGRP over a wide dose range. In addition to demonstrating an agonist-like effect for CGRP (8-37), these data also indicate that CGRP and CGRP (8-37) may not act through a common mechanism.
Department of Pharmacology & Toxicology Medical College of Virginia/Virginia Commonwealth University Richmond 23298-0613.
M A
MA
Saxen
F L
FL
Smith
L D
LD
Dunlow
D S
DS
Dombrowski
S P
SP
Welch
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply
D000700:Analgesics; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide