Behavioral, pharmacological, and molecular characterization
of an amphibian cannabinoid receptor
by
Soderstrom K, Leid M, Moore FL, Murray TF
College of Pharmacy.
Department of Zoology,
Oregon State University,
Corvallis, Oregon, USA.
soderstrom@psy.fsu.edu
J Neurochem 2000 Jul; 75(1):413-23
ABSTRACTInvestigation of cannabinoid pharmacology in a vertebrate with a phylogenetic history distinct from that of mammals may allow better understanding of the physiological significance of cannabinoid neurochemistry. Taricha granulosa, the roughskin newt, was used here to characterize an amphibian cannabinoid receptor. Behavioral experiments demonstrated that the cannabinoid agonist levonantradol inhibits both newt spontaneous locomotor activity and courtship clasping behavior. Inhibition of clasping was dose-dependent and potent (IC(50) = 1.2 microgram per animal). Radioligand binding studies using [(3)H]CP-55940 allowed identification of a specific binding site (K(D) = 6.5 nM, B(max) = 1,853 fmol/mg of protein) in brain membranes. Rank order of affinity of several ligands was consistent with that reported for mammalian species (K(D), nM) : CP-55940 (3.8) > levonantradol (13.0) > WIN55212-2 (25.7) >> anandamide (1,665) approximately anandamide 100 microM phenylmethylsulfonyl fluoride (2,398). The cDNA encoding the newt CB1 cannabinoid receptor was cloned, and the corresponding mRNA of 5.9 kb was found to be highly expressed in brain. A nonclonal Chinese hamster ovary cell line stably expressing the newt CB1 cannabinoid receptor was prepared that allowed demonstration of cannabinoid-mediated inhibition of adenylate cyclase (EC 4.6.1.1) activity. This inhibition was dose-dependent and occurred at concentrations consistent with affinities determined through radioligand binding experiments. The behavioral, pharmacological, and molecular cloning results demonstrate that a CB1 cannabinoid receptor is expressed in the CNS of the roughskin newt. This amphibian CB1 is very similar in density, ligand binding affinity, ligand binding specificity, and amino acid sequence to mammalian CB1. The high degree of evolutionary conservation of cannabinoid signaling systems implies an important physiological role in vertebrate brain function.Aerosol
Memory
Potency
Plants/CNS
Anandamide
Tolerant mice
Just say know
Keen-eyed goldfish
The nectar of delight
Stoned chocaholics?
Humans are not rats
Rodent cannabis abuse
Cannabis-tainted money
Cannabinoids/Parkinson's disease
Cannabinoids as anti-inflammatories01 02 03 04 05 06 07 08 09 10 11 12 13 14 15
Refs
HedWeb
Future Opioids
BLTC Research
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family
