G-RECEPTOR ANTAGONISTS INCREASED THE ACTIVATING EFFECT OF MASTOPARAN ON LOW K-M GTPASE OF MOUSE PAG

Mastoparan activated in a concentration-dependent manner the low K-m G TPase activity in P-2 fractions from mouse periaquedultal grey matter (PAG). This peptide at 1-10 mM produced increases of 30-70% over the b asal value of 90-120 pmol Pi/mg/min. A series of substances displaying antagonist activity al cellular receptors and not modifying the GTPas e function, when used at nanomolar and micromolar concentrations enhan ced the effect of mastoparan upon this enzyme. These included antagoni sts of receptors coupling G proteins: naloxone (non selective opioid a ntagonist), CTOP (m opioid receptors), ICI 174,864 (d opioid receptors ), nor-BNI (k opioid receptors), sulpiride (D-2 dopaminergic antagonis t), idazoxan (a(2) adrenergic antagonist). Bicuculline, antagonist of a receptor not linked to G proteins, GABA(A), did not alter the effect of mastoparan on the GTPase. The m opioid agonist, DAMGO, prevented n aloxone from increasing the function of the mastoparan-activated enzym e. Thus, mastoparan appears to act on G(i)/G(o) proteins at a site not directly related to the receptor binding domain.