Effect of a Cholecystokinin Tetrapeptide Analogue on Opioid Reception under Acute and Chronic Morphine Administration

I. P. Anokhina a , T. V. Proskuryakova a# , Zh. D. Bespalova b , M. E. Palíkeeva b , V. A. Shokhonova a , and O. B. Petrichenko a

# Phone +7 (495) 241-0243, e-mail: pros-lab@mtu-net.ru
a Federal State Unitary Enterprise National Scientific Center on Addictions, Federal Agency on Healthcare and Social Development, M. Mogilítsevskii per. 3, Moscow , 119002, Russia
b Federal State Unitary Enterprise Russian Cardiological Scientific and Production Association, Federal Agency on Healthcare and Social Development, Tret'ya Cherepkovskaya ul. 15a, Moscow , 121552 Russia

Received September 20, 2005; in final form, December 19, 2005

Abstract: Effects of a modified CCK-4, a tetrapeptide fragment of cholecystokinin, on opioid reception and cAMP level were studied. The modified CCK-4 changed the ligand binding of the opioid receptors of μ- and δ-types in vitro. In vivo, it prevented changes in opioid reception caused by an acute morphine administration or by morphine withdrawal after its long-term administration. The CCK-4 analogue did not exert any effect in the state of intoxication after a long-term introduction of morphine or even promoted the morphine effect. The injection of the CCK-4 analogue alone or together with morphine changed the forskolin-stimulated level of cAMP. These changes depended on the brain structure and the duration of the introduction of morphine and the CCK-4 analogue.

Key words: cAMP, cholecystokinin-(30--33) fragment (CCK-4), morphine, opioid receptors

Russian Journal of Bioorganic Chemistry 2006, 32 (3):248-254