The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain

• Published in: Biochemical journal Vol. 267; no. 1; pp. 233 - 240
• Main Authors: Khawaja, X Z, Green, I C, Thorpe, J R, Titheradge, M A
• Format: Journal Article
• Language: English
• Published: England 01-04-1990
• Subjects: Animals; beta-Endorphin - metabolism; Brain - metabolism; Dynorphins - metabolism; Endorphins - metabolism; Enkephalin, Ala-MePhe-Gly; Enkephalin, Leucine - analogs & derivatives; Enkephalin, Leucine - metabolism; Enkephalin, Leucine-2-Alanine - analogs & derivatives; Enkephalin, Methionine - metabolism; Enkephalins - metabolism; Female; Immunohistochemistry; Liver - metabolism; Male; Pancreas - metabolism; Radioimmunoassay; Radioligand Assay; Rats; Rats, Inbred Strains; Receptors, Opioid - metabolism; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2670233

Our observations that opioid peptides have direct effects on islet insulin secretion and liver glucose production prompted a search for endogenous opiates and their receptors in these peripheral tissues. Mu-, delta- and kappa-receptor-active opiates were demonstrated in brain, pancreas and liver extracts by displacement studies using selective ligands for the three opiate receptor subtypes [( 3H][D-Ala2,MePhe4,Gly5-ol]enkephalin, [3H][D-Ala2,D-Leu5]enkephalin and [3H]dynorphin respectively). Receptor-active opiates in brain extracts exhibited a stronger preference for delta-opiate-receptor sites than for mu and kappa sites. Pancreatic extract opiates demonstrated a similar activity at mu and delta sites, but substantially less at kappa sites. Liver extracts displayed similar selectivity for all three sites. The affinities of the receptor-active opiates for mu-, delta- and kappa-receptor subtypes displayed a rank order of potency: brain much greater than pancreas greater than liver. Total immunoreactive beta-endorphin and [Met5]enkephalin levels in liver and hepatocytes were greater than those in brain. Immunoreactive [Met5]enkephalin levels in pancreas were similar to, but beta-endorphin levels were substantially higher than, those in brain. Delta and kappa opiate-binding sites of high affinity were identified in crude membrane preparations of islets of Langerhans, but no specific opiate-binding sites could be demonstrated in liver membrane preparations. Immunoreactive dynorphin and beta-endorphin were demonstrated by immunogold labelling in rat pancreatic islet cells. No positive staining of liver sections for opioids was observed. These results suggest that the tissue content of opiate-receptor-active compounds in the pancreas and the liver is very significant and could contribute to the regulation of normal blood glucose levels.