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Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart.
J Pharmacol Exp Ther. 1990 Mar; 252(3):1075-82.JP

Abstract

The studies in this report were carried out to investigate the effects of delta 9-tetrahydrocannabinol (delta 9-THC) on cardiac membrane adenylate cyclase activity and to determine the role of changes in membrane lipid order in these effects. delta 9-THC and its psychoactive metabolite, 11-OH-delta 9-THC, increased isoproterenol (ISO) stimulation of adenylate cyclase in rat cardiac ventricular membranes. Cannabidiol, cannabinol and (+)-delta 9-THC were all without effect, indicating that this effect of delta 9-THC is stereoselective and specific for cannabinoids with psychoactive potency. delta 9-THC also increased glucagon stimulation of adenylate cyclase. The enhancement of both ISO and glucagon-stimulated adenylate cyclase was due to an increase in the Vmax of these agonists with no significant change in Kact. delta 9-THC did not affect basal adenylate cyclase activity or the activation of the enzyme by forskolin, guanine nucleotides or fluoride ion. Those cannabinoids which increased ISO-stimulated adenylate cyclase activity also decreased the break temperature of the Arrhenius plot; evidence that the effects of delta 9-THC involve changes in membrane phospholipid order. The effects of the cannabinoids on cardiac membrane phospholipid order were investigated directly using diphenylhexatriene fluorescence polarization. delta 9-THC and 11-OH-delta 9-THC alone decreased the break temperature of the diphenylhexatriene temperature profile, i.e., decreased the temperature of the lipid phase separation. This effect of delta 9-THC was stereoselective.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

2156989

Citation

Hillard, C J., et al. "Studies of the Role of Membrane Lipid Order in the Effects of Delta 9-tetrahydrocannabinol On Adenylate Cyclase Activation in Heart." The Journal of Pharmacology and Experimental Therapeutics, vol. 252, no. 3, 1990, pp. 1075-82.
Hillard CJ, Pounds JJ, Boyer DR, et al. Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart. J Pharmacol Exp Ther. 1990;252(3):1075-82.
Hillard, C. J., Pounds, J. J., Boyer, D. R., & Bloom, A. S. (1990). Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart. The Journal of Pharmacology and Experimental Therapeutics, 252(3), 1075-82.
Hillard CJ, et al. Studies of the Role of Membrane Lipid Order in the Effects of Delta 9-tetrahydrocannabinol On Adenylate Cyclase Activation in Heart. J Pharmacol Exp Ther. 1990;252(3):1075-82. PubMed PMID: 2156989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart. AU - Hillard,C J, AU - Pounds,J J, AU - Boyer,D R, AU - Bloom,A S, PY - 1990/3/1/pubmed PY - 1990/3/1/medline PY - 1990/3/1/entrez SP - 1075 EP - 82 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 252 IS - 3 N2 - The studies in this report were carried out to investigate the effects of delta 9-tetrahydrocannabinol (delta 9-THC) on cardiac membrane adenylate cyclase activity and to determine the role of changes in membrane lipid order in these effects. delta 9-THC and its psychoactive metabolite, 11-OH-delta 9-THC, increased isoproterenol (ISO) stimulation of adenylate cyclase in rat cardiac ventricular membranes. Cannabidiol, cannabinol and (+)-delta 9-THC were all without effect, indicating that this effect of delta 9-THC is stereoselective and specific for cannabinoids with psychoactive potency. delta 9-THC also increased glucagon stimulation of adenylate cyclase. The enhancement of both ISO and glucagon-stimulated adenylate cyclase was due to an increase in the Vmax of these agonists with no significant change in Kact. delta 9-THC did not affect basal adenylate cyclase activity or the activation of the enzyme by forskolin, guanine nucleotides or fluoride ion. Those cannabinoids which increased ISO-stimulated adenylate cyclase activity also decreased the break temperature of the Arrhenius plot; evidence that the effects of delta 9-THC involve changes in membrane phospholipid order. The effects of the cannabinoids on cardiac membrane phospholipid order were investigated directly using diphenylhexatriene fluorescence polarization. delta 9-THC and 11-OH-delta 9-THC alone decreased the break temperature of the diphenylhexatriene temperature profile, i.e., decreased the temperature of the lipid phase separation. This effect of delta 9-THC was stereoselective.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2156989/Studies_of_the_role_of_membrane_lipid_order_in_the_effects_of_delta_9_tetrahydrocannabinol_on_adenylate_cyclase_activation_in_heart_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2156989 DB - PRIME DP - Unbound Medicine ER -