alpha N-acetyl-beta-endorphin-(1-31) disrupts the diminishing effect of mastoparan on opioid- and clonidine-evoked supraspinal antinociception in mice.
Intracerebroventricular (i.c.v.) administration to mice of the venom tetradecapeptide mastoparan (MP), which binds certain G transducer proteins, resulted in a long-lasting reduction of the supraspinal antinociception induced by opioids and clonidine, the alpha-2 adrenoceptor agonist. The alpha N-acetyl derivative of beta-endorphin-(1-31) (NAC-beta-END; 1 pmol, i.c.v. per mouse) injected 1 hr before an equimolar dose of MP lessened the antagonist activity of the venom peptide on the antinociception induced by D-pen2,5-enkephalin, [D-Ala2]deltorphin II, D-Ala2-N-MePhe4-Gly-ol5-enkephalin and clonidine when evaluated 24 hr later with the tail-flick test. The impairment exerted by MP on these analgesic substances was not altered when NAC-beta-END was administered after the venom peptide. Therefore, the antinociceptive effect depends on which peptide was injected first. The protective activity of NAC-beta-END against MP antagonism of opioid/clonidine antinociception was dose related and exerted at attomolar and femtomolar doses. This finding strengthens the idea of a neural substrate (possibly G proteins) distinct from the opioid receptor enacted by NAC-beta-END to modulate opioid/clonidine antinociception. This research shows that a series of substances, neuropeptides and venoms dissimilarly influence the functional state of G proteins, thus altering the agonist-activated transduction cascade.
Sánchez-Blázquez
P
P
Instituto Cajal, C.S.I.C., Madrid, Spain.
Garzón
J
J
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D013131:Spine; D014862:Wasp Venoms / Q000037:antagonists & inhibitors*; D001615:beta-Endorphin / Q000031:analogs & derivatives*
D000701:Analgesics, Opioid; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D018341:Receptors, Adrenergic, alpha-2; D014862:Wasp Venoms; D001615:beta-Endorphin; C037500:mastoparan; D003000:Clonidine