The effects of intrathecal galanin message-associated peptide (GMAP) on the flexor reflex in rats.
We have examined the effects of intrathecal (i.t.) galanin message-associated peptide (GMAP), the C-terminal flanking peptide in the galanin (GAL) precursor protein, which is produced in equimolar quantities with galanin and which is upregulated upon axotomy, on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. I.t. GMAP elicited a moderate facilitation of the flexor reflex. No depression of baseline flexor reflex was observed with any dose of GMAP. The facilitation of the flexor reflex induced by conditioning stimulation (CS) of cutaneous C-afferents was dose-dependently blocked by GMAP. The reflex facilitatory effect of exogenously applied substance P (SP), one of the endogenous modulators of reflex hyperexicitability following C-fiber CS, was only blocked by GMAP at a relatively high dose. I.t. GMAP did not antagonize the reflex facilitatory effect of vasoactive intestinal peptide and did not potentiate the reflex depressive effect of i.t. morphine or clonidine. Finally, 1 micrograms i.t. GMAP did not influence spinal cord blood flow whereas 10 micrograms GMAP induced a transient decrease in spinal cord blood flow in some experiments. The ability of GMAP to block the increase in spinal cord excitability following repetitive C-fiber stimulation may be through a presynaptic action. Although some of the effects of GMAP were similar to galanin, distinct differences were found, particularly in interaction with other excitatory and inhibitory agents. It is possible that GMAP exerts its action in the spinal cord through its own specific receptor. GMAP may act similarly to GAL in some, but not all pharmacological functions.(ABSTRACT TRUNCATED AT 250 WORDS)
Xu
X J
XJ
Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Karolinska Institute, Sweden.
Andell
S
S
Hao
J X
JX
Wiesenfeld-Hallin
Z
Z
Bartfai
T
T
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D005260:Female; D019004:Galanin / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012867:Skin / Q000166:cytology / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology
D000701:Analgesics, Opioid; D010446:Peptide Fragments; D011498:Protein Precursors; D013565:Sympatholytics; C078371:galanin message-associated peptide; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D009020:Morphine; D019004:Galanin; D003000:Clonidine