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The effects of charge-neutralizing mutation D6.30N on the functions of CB1 and CB2 cannabinoid receptors.
FEBS Lett. 2006 Oct 02; 580(22):5392-8.FL

Abstract

Charge-neutralizing mutation D6.30N of the human cannabinoid receptor subtype 1 (CB1) and cannabinoid receptor subtype 2 (CB2) cannabinoid receptors was made to test two hypotheses: (1) D6.30 may be crucial for the functions of CB1 and CB2 receptors. (2) D6.30 may participate in an ionic lock with R3.50 that keeps the receptors in an inactive conformation. Specific ligand binding and ligand-induced inhibition of forskolin-stimulated cAMP accumulation were observed with human embryonic kidney epithelial cell line (HEK293) cells expressing wild-type CB1 and CB2, as well as CB1D6.30N and CB2D6.30N mutant receptors. There was however a decrease in maximum response of the mutant receptors compared to their wild-type counterparts, suggesting that D6.30 is essential for full activation of both CB1 and CB2 receptors. Both CB1D6.30N and CB2D6.30N demonstrated a level of constitutive activity no greater than that of their wild-type counterparts, indicating that either D6.30 does not participate in a salt bridge with R3.50, or the salt bridge is not critical for keeping cannabinoid receptors in the inactive conformation.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, School of Medicine University of Louisville, KY 40292, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16989818

Citation

Nebane, Ntsang M., et al. "The Effects of Charge-neutralizing Mutation D6.30N On the Functions of CB1 and CB2 Cannabinoid Receptors." FEBS Letters, vol. 580, no. 22, 2006, pp. 5392-8.
Nebane NM, Kellie B, Song ZH. The effects of charge-neutralizing mutation D6.30N on the functions of CB1 and CB2 cannabinoid receptors. FEBS Lett. 2006;580(22):5392-8.
Nebane, N. M., Kellie, B., & Song, Z. H. (2006). The effects of charge-neutralizing mutation D6.30N on the functions of CB1 and CB2 cannabinoid receptors. FEBS Letters, 580(22), 5392-8.
Nebane NM, Kellie B, Song ZH. The Effects of Charge-neutralizing Mutation D6.30N On the Functions of CB1 and CB2 Cannabinoid Receptors. FEBS Lett. 2006 Oct 2;580(22):5392-8. PubMed PMID: 16989818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of charge-neutralizing mutation D6.30N on the functions of CB1 and CB2 cannabinoid receptors. AU - Nebane,Ntsang M, AU - Kellie,Brandon, AU - Song,Zhao-Hui, Y1 - 2006/09/12/ PY - 2006/07/05/received PY - 2006/08/30/revised PY - 2006/09/01/accepted PY - 2006/9/23/pubmed PY - 2006/11/11/medline PY - 2006/9/23/entrez SP - 5392 EP - 8 JF - FEBS letters JO - FEBS Lett VL - 580 IS - 22 N2 - Charge-neutralizing mutation D6.30N of the human cannabinoid receptor subtype 1 (CB1) and cannabinoid receptor subtype 2 (CB2) cannabinoid receptors was made to test two hypotheses: (1) D6.30 may be crucial for the functions of CB1 and CB2 receptors. (2) D6.30 may participate in an ionic lock with R3.50 that keeps the receptors in an inactive conformation. Specific ligand binding and ligand-induced inhibition of forskolin-stimulated cAMP accumulation were observed with human embryonic kidney epithelial cell line (HEK293) cells expressing wild-type CB1 and CB2, as well as CB1D6.30N and CB2D6.30N mutant receptors. There was however a decrease in maximum response of the mutant receptors compared to their wild-type counterparts, suggesting that D6.30 is essential for full activation of both CB1 and CB2 receptors. Both CB1D6.30N and CB2D6.30N demonstrated a level of constitutive activity no greater than that of their wild-type counterparts, indicating that either D6.30 does not participate in a salt bridge with R3.50, or the salt bridge is not critical for keeping cannabinoid receptors in the inactive conformation. SN - 0014-5793 UR - https://www.unboundmedicine.com/medline/citation/16989818/The_effects_of_charge_neutralizing_mutation_D6_30N_on_the_functions_of_CB1_and_CB2_cannabinoid_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-5793(06)01066-0 DB - PRIME DP - Unbound Medicine ER -