Discrimination of three types of opioid binding sites in rat brain in vivo

JS Rosenbaum, NH Holford, ML Richards, RA Aman and W Sadee

Opiate receptor sites in the rat brain were defined in vivo by measuring the binding of etorphine, sufentanil, diprenorphine, and naloxone in saturation and cross-competition experiments. The binding data were analyzed simultaneously, using a computerized curve-fitting technique with an extended least-squares nonlinear regression program. Three types of binding sites could be distinguished: site 1 (18 pmoles/g of brain), site 2 (15 pmoles/g of brain), and site 3 (20 pmoles/g of brain). Site 1 is bound selectively by sufentanil (the ratio of the apparent equilibrium dissociation constants K2/K1 approximately equal to 1200), etorphine (K2/K1 approximately equal to 20), and naloxone (K2/K1 approximately equal to 15), and it resembles the mu binding site previously demonstrated in vitro. Diprenorphine binds to both site 1 and site 2 with high affinity and a slight (approximately 3.7-fold) selectivity for site 1 over site 2. The latter site may represent a mixture of the delta and kappa binding sites. The third site displays relatively high affinity for naloxone, but it is clearly different from sites 1 and 2, as it exhibits a lack of affinity for sufentanil, etorphine, and diprenorphine. This binding site population does not resemble any of the known opiate binding sites. Recent in vitro binding studies revealed that site 3 (now termed lambda site) is highly labile in vitro and was, therefore, not previously detected. These results suggest significant differences between in vitro and in vivo opioid receptor binding characteristics.

Volume 25, Issue 2, pp. 242-248, 03/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				H. S. Moeniralam, E. Endert, M. T. Ackermans, J. J. B. Van Lanschot, H. P. Sauerwein, and J. A. Romijn The opiate sufentanil alters the inflammatory, endocrine, and metabolic responses to endotoxin in dogs Am J Physiol Endocrinol Metab, September 1, 1998; 275(3): E440 - E447. [Abstract] [Full Text] [PDF]