Effects of Putative Calmodulin Antagonists on the B nding of [3H]Opioid Ligands to Rat Brain Membranes: Possible Involvement of the Change in the Membrane Fluidity

• Published in: Japanese journal of pharmacology 1986, Vol.42 (2), p.159-167
• Main Authors: MARUYAMA, Mutsumi, AKITA, Kyoko
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.42.159

The effects of putative calmodul n antagonists on the binding of [3H]- opioid ligands to rat brain membranes were examined. Chlorpromazine, trifluoperazine, N-(6-aminohexyl)-5-chloro-1 -naphthalenesulfonamide (W-7) and N2-dansyl-L-arginine-4-t-butylpiperidine amide (Tl 233, No. 233) inhibited the binding of [3H] [D-Ala2, Met5]enkephalinamide ([3H]DALAMID) in a dose- dependent manner, and this inhibition was not necessarily specific for Ca2+. The order of the inhibitory potency on the binding of [3H] DALAMID was chlorpromazine, W-7, TI 233 and trifluoperazine. From the Scatchard plots, the effects of these compounds on the binding of [3FI]DALAMID were biphasic. Low concentrations of calmodulin antagonists caused a small but significant increase in the maximal binding (Bmax), but upon a further increase of the concentration, a significant decrease in Bmax was observable; the apparent dissociation constant for the ligand- receptor complexes increased with the increase in the concentration of calmodulin antagonists. TI 233 (1–30×10−6 M) inhibited, somewhat in a ligand selective manner, the binding of [3H]opioid ligands that have been thought to be selective for opioid receptor types. Calmodulin antagonists caused to increase in the fluorescence anisotropy obtained from 1,6-diphenyl-1,3,5-hexatriene-labeled membrane fractions from rat brains, indicating that these compounds were effective for the decrease in the membrane fluidity. The present results indicate that putative calmodulin antagonists can affect the binding of the opioid ligands to rat brain membranes, probably through a mechanism other than one involving calmodulin- related processes.