The gamma(2)-MSH peptide mediates a central analgesic effect via a GABA-ergic mechanism that is independent from activation of melanocortin receptors.
Using the latency for tail-flick after thermal stimulation we have assessed the effects of alpha-, gamma(1)- and gamma(2)-MSH on nociceptive threshold in the mice. Intracisternal injections of gamma(2)-MSH induced a distinct analgesia, while gamma(1)-MSH in the same doses gave only a minor analgesia. Intracisternal alpha-MSH instead gave a short-term hyperalgesia. The effect of gamma(2)-MSH was not blocked by any of the MC(4)/MC(3)receptor antagonist HS014, naloxone or by the prior intracisternal administrations of gamma(1)-MSH. However, the gamma(2)-MSH analgesic response was completely attenuated by treating animals with the GABA(A)antagonist bicuculline. The gamma(2)-MSH analgesic effect was moreover additive to the analgesia afforded by muscimol and ethanol, but not to that afforded by diazepam. In addition both gamma(1)- and gamma(2)-MSH induced moderate catalepsy, but could at the same time attenuate haloperidol induced catalepsia. We conclude that gamma(2)-MSH mediates a central analgesic effect via GABA-receptor dependent pathway that is distinct from melanocortic- and opioid-receptors. Moreover, the mechanism for gamma(2)-MSH's analgesic effect appears to be distinct from that causing moderate catalepsia by gamma-MSH's.
Klusa
V
V
1Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga, Latvia.
Germane
S
S
Svirskis
S
S
Opmane
B
B
Wikberg
J E
JE
D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D018043:Receptors, Corticotropin / Q000378:metabolism*; D044101:Receptors, Melanocortin; D013623:Tail; D000521:alpha-MSH / Q000378:metabolism / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D019825:gamma-MSH / Q000378:metabolism / Q000494:pharmacology*
D000700:Analgesics; D002492:Central Nervous System Depressants; D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; C116941:HS014 cyclic peptide; D009292:Narcotic Antagonists; D010456:Peptides, Cyclic; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D019825:gamma-MSH; D009118:Muscimol; D009270:Naloxone; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000521:alpha-MSH; D003975:Diazepam; D001640:Bicuculline