Effects of a centipede venom fraction on insect nervous system, a native Xenopus oocyte receptor and on an expressed Drosophila muscarinic receptor

Centipede venoms are complex protein mixtures; very few is known about thei r pharmacological actions. Application of a Scolopendra sp. venom fraction (SC1) on the cockroach giant axon induced an increase in the leak current c orrelated with a decrease in the membrane resistance, suggesting the presen ce in SC1 of components opening nonspecific pores in the axonal membrane. O n a cockroach central cholinergic synapse. microinjection of SC1 induced a small transient depolarization of the postsynaptic membrane, followed by a slow stable depolarization and a drastic decrease in the evoked subthreshol d excitatory postsynaptic potential amplitude. A pretreatment of the gangli on with atropine or scopolamine reduced the amplitude of the SC1-induced de polarizing wave, suggesting a possible cholinergic muscarinic target. On co ntrol Xenopus oocytes, SC1 induced an inward oscillatory Ca2+-dependent Cl- current mediated through the activation of native lysophosphatidic acid re ceptors (LPAr). Indeed, pretreatment of oocytes with 1 mu M N-palmitoyl-tyr osine phosphoric acid, a selective competitive antagonist of LPAr, decrease d responses to SC1 by 70%. Application of SC1 to oocytes expressing a clone d Drosophila muscarinic receptor (Dm1) induced a biphasic response comprisi ng: (1) a large fast Cl- current that was abolished by pretreatment with at ropine and scopolamine and (2) a slow and small oscillating Cl- current cor responding to the response observed in control oocytes. These observations confirm the presence of muscarinic agonists in SC1 and reveal their direct action on an insect muscarinic receptor subtype homologous to mammalian M1- M3 receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.