Enkephalins, endogenous
opioid pentapeptides which are found in high concentration in normal chromaffin tissue, may play a role in blood pressure regulation. We therefore examined the presence and actions of
enkephalins in
pheochromocytoma in a rat model. Transplantable
norepinephrine-rich
tumors, which gave rise to significant blood pressure elevations, contained measurable immunoreactive
enkephalins as determined by specific radioimmunoassays for
leucine-enkephalin and
methionine-enkephalin.
Enkephalin immunoreactivity paralleled the
enkephalin assay standard curves and was not abolished by boiling or by
protease inhibitors (
EDTA, PMSF). Authenticity of the immunoreactive
enkephalins was confirmed by reverse-phase high pressure liquid chromatography. The amount of
enkephalin immunoreactivity present initially in these
tumors was greatly augmented by the prohormone activators
trypsin or
trypsin plus
carboxypeptidase B, suggesting that most of the immunoreactive
enkephalin was present in higher molecular weight precursor form.
Enkephalin determinations on human
pheochromocytoma and
catecholamine measurements in both rat and human
pheochromocytoma, demonstrated certain similarities and differences in
enkephalin and
catecholamine content between rat and human
tumors. Total
tumor enkephalins correlated (r = 0.91, p less than 0.05) with total
tumor catecholamines in rat
pheochromocytoma, suggesting co-regulation of synthesis of these 2 chromaffin tissue substances. Physiologic studies, in which intravenous
leucine-enkephalin and the
opioid antagonist nalaxone were administered to
pheochromocytoma-implanted rats and
sham-operated controls, failed to uncover an
opioid peptide influence upon blood pressure in this animal model of
pheochromocytoma.