Could dual G-protein coupling explain [D-Met2]FMRFamide's mixed action in vivo?
In vitro studies have demonstrated that FMRFamide-related peptide receptors can be coupled to different G-proteins, mediating opposite stimulatory and inhibitory effects. The present study tested whether this duality might extend to effects in vivo. Antinociception in mice of ICV [D-Met2]FMRFamide, which produced agonist [ED50 = 36.3 micrograms (61.6 nmol)] and antagonist [ID50 = 0.72 microgram (1.22 nmol)] actions, was attenuated by 24-h pretreatment with ICV pertussis toxin (ID50 = 0.55 microgram) or cholera toxin (ID50 = 0.09 microgram), suggesting that [D-Met2]FMRFamide in vivo effects might also be explained by dual Gi/Gs, coupling.
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Drug Discovery, R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D019835:FMRFamide; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009479:Neuropeptides; D010566:Virulence Factors, Bordetella; D009270:Naloxone; D019835:FMRFamide; D009020:Morphine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins