Are opioid peptides co-transmitters in noradrenergic vesicles of sympathetic nerves?

Abstract

Biogenic amines and peptide hormones co-exist in paraneurones1 or amine precursor uptake and decarboxylation (APUD) cells2. Opioid peptide immunohistofluorescence occurs in the gland cells and nerve endings of the adrenal medulla3, and both dopamine β-hydroxylase (EC 1.14.17.1) and enkephalin-like immunohistofluorescence occurs in some small intensely fluorescent and sympathetic ganglion cells4. Direct biochemical assays demonstrate opiate-like peptides (OLPs) including Met- and Leu-enkephalin in the adrenal medulla, and the highest specific activity is attained in the purified adrenomedullary chromaffin granule fraction5. Chromaffin cells also synthesize enkephalins de novo6. Adrenal medullae from larger species, including ox and man, contain much more OLP material than those from smaller species such as rodents5,7; fortunately so, because only from ox is it practical to purify both chromaffin granules and splenic nerve vesicles at particle purity and yield suitable for chemical composition studies. In ox and man the large dense-cored vesicles (LDVs) comprise 30–50% of the vesicle population in terminals of blood vessels, spleen and vas deferens, equivalent to 80–90% of the total terminal vesicle capacity. For these reasons, we chose bovine splenic nerve in which to investigate the localization of OLPs in the peripheral sympathetic system. Our results, reported here and based on direct biochemical analyses, indicate that OLPs, putative transmitters and noradrenaline probably coexist in sympathetic C-fibres, which constitute 98% of the bovine splenic nerve. Further, the OLPs and noradrenaline can probably co-exist in the large dense-cored noradrenergic vesicles of this nerve. We believe the obtained 1:60 molar ratio of opioid peptides:noradrenaline to be the highest yet demonstrated for enkephalins in any neurotransmitter organelle or tissue.