Release of calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal polypeptide (VIP) from rat spinal cord: modulation by alpha 2 agonists.
Release of calcitonin gene-related peptide (CGRP) and substance P (SP) from the rat lumbar dorsal spinal cord and vasoactive intestinal polypeptide (VIP) from the sacral spinal cord was examined under resting conditions (baseline release) and in the presence of capsaicin (CAP). Baseline rates of CGRP, SP, and VIP release were 1.71 +/- 0.19, 0.12 +/- 0.01, and 0.097 +/- 0.029 pg/mg/min, respectively. The addition of CAP (10 microM) to the perfusate had no effect upon resting VIP release, but elevated CGRP and SP release significantly by 11.1 +/- 0.8 and 0.19 +/- 0.03 pg/mg/min over baseline release rate, respectively. Addition of dexmedetomidine (10 microM), an alpha 2-adrenergic agonist, did not change the baseline release of either CGRP or SP, but significantly decreased the CAP-evoked release of both peptides. The attenuation of the CAP-evoked release by the agonists was antagonized by the concurrent administration of yohimbine (10 microM) or atipamezole (10 microM), but not by prazosin. ST-91 (10 microM) did not alter the release of CGRP but decreased the CAP-evoked release of SP. This inhibition was antagonized by yohimbine and prazosin, but not by atipamezole. These data suggest that the afferent-evoked release of SP and CGRP from CAP-sensitive terminals (presumably those associated with small primary afferents) is modulated by local alpha 2 receptors. The common sensitivity of the agonists to yohimbine and the differential effects of atipamezole and prazosin are consistent with the hypothesis that dexmedetomidine and ST-91 may interact with different subpopulations of spinal alpha 2 receptors, both of which may modulate afferent terminal release.(ABSTRACT TRUNCATED AT 250 WORDS)
Takano
M
M
Department of Anesthesiology, University of California, San Diego, La Jolla 92093.
Takano
Y
Y
Yaksh
T L
TL
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D020926:Medetomidine; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; C011266:ST 91; D015740:Calcitonin Gene-Related Peptide; D003000:Clonidine; D020926:Medetomidine; D002211:Capsaicin