Local anesthetics inhibit receptor coupled to phosphoinositide signaling in Xenopus oocytes

József Tigyi, Gabor Tigyi, Károly Liliom, Ricardo Miledi

Research output: Contribution to journalArticle

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Abstract

Effects and the mechanism of action of quaternary amine local anesthetics on ligand- and voltage-activated ion cut-rents were studied using voltage-clamped ovarian follicles and oocytes from Xenopus laevis. The fast inward and slow outward currents in response to acetylcholine were unaltered by procaine, whereas the oscillatory and smooth inward chloride currents (I(Cl)) were abolished. Potassium currents (I(K)) elicited by norepinephrine and oscillatory I(Cl) elicited by lysophosphatidic acid were blocked. Procaine caused a noncompetitive inhibition of oscillatory I(Cl) mediated by heterologously expressed neurotransmitter receptors from the rat brain. Threefold differences were found in the procaine sensitivity of the 5-HT(2a) and 5-HT(2c) receptors. The rank order of intrinsic inhibitory activity of local anesthetics was: procaine > lidocaine > dibucaine > tetracaine. Extra- or intracellular application of procaine did not alter the Ca2+-activated Cl- current, indicating that neither the endogenous voltage-gated Ca2+ nor the Ca2+ activated Cl- channels account for the inhibition. Procaine caused only a slight reduction in I(Cl) elicited by photolysis of caged inositol 1,4,5-trisphosphate (InsP3) and did not abolish I(Cl) triggered by GTP[γ-S]-induced direct activation of G proteins. For receptors coupling to the phosphoinositide/Ca2+ signal transduction pathway, the primary and physiologically relevant site of procaine action appears to be on the extracellular surface, upstream from the G protein, presumably on the receptor.

Original languageEnglish (US)
Pages (from-to)478-487
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Volume433
Issue number4
DOIs
StatePublished - Feb 20 1997

Fingerprint

Procaine
Xenopus
Phosphatidylinositols
Local Anesthetics
Oocytes
Chlorides
GTP-Binding Proteins
Electric potential
Dibucaine
Receptor, Serotonin, 5-HT2C
Tetracaine
Signal transduction
Neurotransmitter Receptor
Inositol 1,4,5-Trisphosphate
Ovarian Follicle
Photolysis
Xenopus laevis
Lidocaine
Guanosine Triphosphate
Acetylcholine

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Local anesthetics inhibit receptor coupled to phosphoinositide signaling in Xenopus oocytes. / Tigyi, József; Tigyi, Gabor; Liliom, Károly; Miledi, Ricardo.

In: Pflugers Archiv European Journal of Physiology, Vol. 433, No. 4, 20.02.1997, p. 478-487.

Research output: Contribution to journalArticle

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