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Effects of local anesthetics on guanyl nucleotide modulation of the catecholamine-sensitive adenylate cyclase system and on beta-adrenergic receptors.

Publication ,  Journal Article
Voeikov, VL; Lefkowitz, RJ
Published in: Biochim Biophys Acta
May 7, 1980

Tetracaine and other local anesthetics exert multiple actions on the catecholamine-sensitive adenylate cyclase system of frog erythrocyte membranes. Tetracaine (0.2--20 mM) reduces the responsiveness of adenylate cyclase to (a) guanyl-5'-yl-imidodiphosphate and (b) isoproterenol in the presence of GTP or guanyl-5'-yl-imidodiphosphate. Local anesthetics did not affect (a) basal enzyme activity, and (b) enzyme responsiveness to NaF. Tetracaine inhibited stimulation of adenylate cyclase by guanyl-5'-yl-imidodiphosphate over the whole range of nucleotide concentrations. By contrast, inhibition by tetracaine of isoproterenol activity in the presence of GTP was significant only if GTP concentrations exceeded 10(-7) M. Tetracaine also competitively inhibited binding of both the antagonist [3H]dihydroalprenolol and the agonist [3H]hydroxybenzylisoproterenol to beta-adrenergic receptors. However, it was twice as potent in inhibiting [3H]hydroxybenzylisoproterenol as [3H]dihydroalprenolol binding. The greater potency for inhibition of agonist binding was due to the ability of the anesthetics to promote dissociation of the high-affinity nucleotide sensitive state of the beta-adrenergic receptor induced by agonists. Other local anesthetics mimicked the effects of tetracaine on adenylatecyclase and in dissociating high-affinity agonist-receptor complexes. The other of potency for both processes was dibucaine greater than tetracaine greater than bupivacaine greater than lidocaine which agrees with their relative potencies as local anesthetics. By contrast, a different order of potency was observed for competitive inhibition of [3H]dihydroalprenolol binding: dibucaine greater than tetracaine greater than greater than lidocaine greater than bupivacaine.

Duke Scholars

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

May 7, 1980

Volume

629

Issue

2

Start / End Page

266 / 281

Location

Netherlands

Related Subject Headings

  • Tetracaine
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Isoproterenol
  • In Vitro Techniques
  • Guanine Nucleotides
  • Erythrocyte Membrane
  • Dihydroalprenolol
  • Catecholamines
  • Anura
 

Citation

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MLA
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Voeikov, V. L., & Lefkowitz, R. J. (1980). Effects of local anesthetics on guanyl nucleotide modulation of the catecholamine-sensitive adenylate cyclase system and on beta-adrenergic receptors. Biochim Biophys Acta, 629(2), 266–281. https://doi.org/10.1016/0304-4165(80)90100-2
Voeikov, V. L., and R. J. Lefkowitz. “Effects of local anesthetics on guanyl nucleotide modulation of the catecholamine-sensitive adenylate cyclase system and on beta-adrenergic receptors.Biochim Biophys Acta 629, no. 2 (May 7, 1980): 266–81. https://doi.org/10.1016/0304-4165(80)90100-2.
Voeikov, V. L., and R. J. Lefkowitz. “Effects of local anesthetics on guanyl nucleotide modulation of the catecholamine-sensitive adenylate cyclase system and on beta-adrenergic receptors.Biochim Biophys Acta, vol. 629, no. 2, May 1980, pp. 266–81. Pubmed, doi:10.1016/0304-4165(80)90100-2.

Published In

Biochim Biophys Acta

DOI

ISSN

0006-3002

Publication Date

May 7, 1980

Volume

629

Issue

2

Start / End Page

266 / 281

Location

Netherlands

Related Subject Headings

  • Tetracaine
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Isoproterenol
  • In Vitro Techniques
  • Guanine Nucleotides
  • Erythrocyte Membrane
  • Dihydroalprenolol
  • Catecholamines
  • Anura