Edward L. Smithwick

Evidence for tonic activity of enkephalins in brain and development of systemically active analogues with clinical potential

The origin and physiological role of the various brain endorphins (Hughes, 1975; Terenius and Wahlstrom, 1975; Goldstein, 1975) remains an intriguing question. In particular, the elucidation of the source, manner of synthesis and specific functions of the brain pentapeptides, [Met5]-enkephalin and [Leu5]-enkephalin, provides an exciting challenge to investigators in the field. There is considerable evidence that these endogenous brain peptides are neurotransmitters or neuromodulators in various brain areas (see for example, Frederickson, 1977). They are present in these areas together with stereospecific receptors and immunohistochemical studies have shown that they are localized in nerve terminals and cell bodies. They affect the firing rate of neurons in these particular brain areas by an action on specific receptors and there is a highly effective system in brain for their inactivation.