Morphine: sites of action in guanosine nucleoside pathway.

Abstract

In 1973, based on evidence yielded by morphine binding studies, Pert and Snyder first proposed that the pharmacologic actions of morphine are effected through a reversible binding of the opiate to specific receptors in the central nervous system (CNS). Subsequently, investigators reported several opiate receptor types (Martin et al, 1976; Lord et al, 1977); more recently, evidence for opiate receptor subtypes has also been presented (Pasternak, 1984). Despite these substantial advancements, however, surprisingly little is known concerning the cascade of biochemical events triggered by the binding of opiate alkaloids to receptor sites in the CNS (Miller, 1984). Most studies intended to elucidate the biochemical actions of opiates are primarily concerned with the effects of these compounds on the activities of the various enzymes involved in adenylate nucleoside metabolism (Palmer, 1983). The numerous contradictory reports in this line of research have, however, clearly demonstrated the futility of attempts to correlate opiate activity to brain levels of the adenylate cyclic nucleotide (Wollemann, 1981; Palmer, 1983). Similarly, there is little consensus regarding the effects of opiates on guanylate cyclic nucleotide concentrations, a subject on which comparatively few investigations have thus far been conducted (Palmer, 1983).