G-receptor antagonists increased the activating effect of mastoparan on low Km GTPase of mouse PAG.
Mastoparan activated in a concentration-dependent manner the low Km GTPase activity in P2 fractions from mouse periaquedultal grey matter (PAG). This peptide at 1-10 mM produced increases of 30-70% over the basal value of 90-120 pmol Pi/mg/min. A series of substances displaying antagonist activity at cellular receptors and not modifying the GTPase function, when used at nanomolar and micromolar concentrations enhanced the effect of mastoparan upon this enzyme. These included antagonists of receptors coupling G proteins: naloxone (non selective opioid antagonist), CTOP (m opioid receptors), ICI 174,864 (d opioid receptors), nor-BNI (k opioid receptors), sulpiride (D2 dopaminergic antagonist), idazoxan (a2 adrenergic antagonist). Bicuculline, antagonist of a receptor not linked to G proteins, GABAA, did not alter the effect of mastoparan on the GTPase. The m opioid agonist, DAMGO, prevented naloxone from increasing the function of the mastoparan-activated enzyme. Thus, mastoparan appears to act on Gi/Go proteins at a site not directly related to the receptor binding domain.
Martínez-Peña
Y
Y
Neurofarmacología Instituto Cajal C.S.I.C., Madrid, Spain.
Sánchez-Blázquez
P
P
Garzón
J
J
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D010455:Peptides; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology*
D004745:Enkephalins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011956:Receptors, Cell Surface; D014862:Wasp Venoms; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D009270:Naloxone; D013004:Somatostatin; C037500:mastoparan; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins