Plasma Norepinephrine, Epinephrine and Dopamine Responses to Intracerebral Administration of a Met-Enkephalin Analog, D-Ala²-Met-Enkephalinamide, in Rats

Abstract

Intracisternal (i. c.) administration (25 μg or 42.6 nmol) of the potent met-enkephalin analog, D-ala²-met-enkephalinamide (DALA) in adult male rats increased plasma concentrations of norepinephrine and epinephrine for more than 90 min. Intra-arterial (i.a.) administration of the same or a fourfold larger dose was without any effect. I.e. administration of human β-endorphin (25 μg or 7.25 nmol) produced much greater plasma responses of all three catecholamines than seen with DALA. An i.a. dose of naloxone, which had been shown previously to inhibit the plasma catecholamine responses to β-endorphin, failed to inhibit plasma catecholamine responses to DALA. Also, naloxone alone failed to alter the basal plasma concentrations of the three catecholamines. The data are consistent with an effect of DALA acting at a presently unknown brain site to increase central sympathetic outflow, thus increasing plasma concentrations of norepinephrine and epinephrine. It appears probable that this effect of DALA is mediated at a different opioid receptor and perhaps a different brain site than the effect of β-endorphin to increase central sympathetic outflow.

Opiate receptors and cardiovascular control in conscious SHR and WKY rats.

“…This finding is consistent with recent studies by Van Loon et al 24 -" showing increased sympathetic activity following ICV administration of /3-endorphin or D-Ala 2 -Met 5 -enkephalin in conscious rats. Furthermore, opioid peptides were shown to inhibit the release of NE from nerve endings, synaptosomes, brain slices in vitro, 26 -27 and brain nuclei in vivo.…”