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Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes.
Mol Pharmacol. 1984 Nov; 26(3):532-8.MP

Abstract

Adenylate cyclase in plasma membranes was inhibited by micromolar concentrations of delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol and by levonantradol and desacetyllevonantradol. This inhibition was noncompetitive for stimulation of the enzyme at the prostanoid receptor by prostaglandin E1 or prostacyclin, or at the peptide receptor by secretin or vasoactive intestinal peptide. Forskolin-activated adenylate cyclase was also inhibited by cannabimimetic agents. Inhibition by cannabinoid compounds was neither synergistic nor additive with muscarinic or alpha-adrenergic agents when each was present at maximally inhibitory concentrations. Cannabinoid inhibition was not blocked by atropine, yohimbine, or naloxone, suggesting that muscarinic, alpha 2-adrenergic and certain opiate receptors may not be required for the response. The inhibition of adenylate cyclase was specific for psychoactive cannabinoids, since cannabinol and cannabidiol produced minimal or no response. Inhibition was also stereoselective, since dextronantradol did not produce the response. A biphasic log dose-response curve was observed for each of the cannabinoid drugs, such that reversal of the inhibition occurred at 3-10 microM. Possible mechanisms for the effects of cannabinoid drugs on adenylate cyclase activity are discussed.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

6092901

Citation

Howlett, A C., and R M. Fleming. "Cannabinoid Inhibition of Adenylate Cyclase. Pharmacology of the Response in Neuroblastoma Cell Membranes." Molecular Pharmacology, vol. 26, no. 3, 1984, pp. 532-8.
Howlett AC, Fleming RM. Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. Mol Pharmacol. 1984;26(3):532-8.
Howlett, A. C., & Fleming, R. M. (1984). Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. Molecular Pharmacology, 26(3), 532-8.
Howlett AC, Fleming RM. Cannabinoid Inhibition of Adenylate Cyclase. Pharmacology of the Response in Neuroblastoma Cell Membranes. Mol Pharmacol. 1984;26(3):532-8. PubMed PMID: 6092901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. AU - Howlett,A C, AU - Fleming,R M, PY - 1984/11/1/pubmed PY - 1984/11/1/medline PY - 1984/11/1/entrez SP - 532 EP - 8 JF - Molecular pharmacology JO - Mol Pharmacol VL - 26 IS - 3 N2 - Adenylate cyclase in plasma membranes was inhibited by micromolar concentrations of delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol and by levonantradol and desacetyllevonantradol. This inhibition was noncompetitive for stimulation of the enzyme at the prostanoid receptor by prostaglandin E1 or prostacyclin, or at the peptide receptor by secretin or vasoactive intestinal peptide. Forskolin-activated adenylate cyclase was also inhibited by cannabimimetic agents. Inhibition by cannabinoid compounds was neither synergistic nor additive with muscarinic or alpha-adrenergic agents when each was present at maximally inhibitory concentrations. Cannabinoid inhibition was not blocked by atropine, yohimbine, or naloxone, suggesting that muscarinic, alpha 2-adrenergic and certain opiate receptors may not be required for the response. The inhibition of adenylate cyclase was specific for psychoactive cannabinoids, since cannabinol and cannabidiol produced minimal or no response. Inhibition was also stereoselective, since dextronantradol did not produce the response. A biphasic log dose-response curve was observed for each of the cannabinoid drugs, such that reversal of the inhibition occurred at 3-10 microM. Possible mechanisms for the effects of cannabinoid drugs on adenylate cyclase activity are discussed. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/6092901/Cannabinoid_inhibition_of_adenylate_cyclase__Pharmacology_of_the_response_in_neuroblastoma_cell_membranes_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6092901 DB - PRIME DP - Unbound Medicine ER -