Morphine (5 mg/kg, s.c.) caused a submaximal increase in the brain level of sodium fluorescein administered i.v. Histamine H1-antagonists, diphenhydramine and mepyramine, given either i.p. or i.c.v., had no significant influence on the effect of morphine. H2-Antagonists, cimetidine and ranitidine, administered i.c.v., but not i.p., significantly inhibited the morphine effect. alpha-Fluoromethylhistidine, a specific histidine decarboxylase inhibitor (given i.p. and i.c.v.) and antimuscarinic drugs, atropine and biperiden, but not methylatropine (given i.p.) also significantly reduced the morphine effect. Physostigimine (i.p.) significantly enhanced the effects of 0.5 and 1 mg/kg of morphine. Similar effects of histaminergic and cholinergic drugs were also observed on the buprenorphine- and DAGO-induced increase in blood-brain barrier (BBB) permeability to sodium fluorescein. None of the treatments with 6-hydroxydopamine, alpha-methyltyrosine, 5,7-dihydroxytryptamine or p-chlorophenylamine had any significant effect on the morphine-induced increase in BBB permeability. These findings suggest that the activation of brain H2-receptors by neuronal histamine and muscarinic receptors by acetylcholine is involved in the increase in BBB permeability to sodium fluorescein caused by mu opioid receptor agonists.

Acetylcholine↗

PubMedDate not supplied

Effects of rat hepatocytes on macromolecular permeability of bovine aortic endothelial cell monolayer.

The aim of this study was to examine whether the hyperpermeable structure of the liver endothelium in vivo is related to the interactions of hepatocytes in a culture system. The permeation of macromolecular FITC-labeled dextran (molecular weight 70,000) through a monolayer of bovine aortic endothelial cells (BAEC), cocultured with rat parenchymal hepatocytes (P-hep), was increased. When the BAEC were cocultured with nonparenchymal hepatocytes (N-hep), the permeability of the BAEC monolayer was not increased. However, when the BAEC were cocultured with a mixture of P-hep and N-hep (PN-hep), the BAEC monolayer was more permeable than when BAEC were cocultured with P-hep alone. The conditioned medium of P-hep did not alter the BAEC monolayer permeability, nor did the extracellular matrix of P-hep alter BAEC permeability. When the BAEC were cocultured with PN-hep, the F-actin content was not altered. These findings suggest that the interaction between hepatocytes and endothelial cells exerts an important effect on the hyperpermeable structure of the liver vessels in vivo.

Actins↗

PubMedDate not supplied

cDNA cloning, tissue distribution, and subcellular localization of horseshoe crab big defensin.

A full-length cDNA for horseshoe crab big defensin with a strong antimicrobial activity was obtained from a hemocyte cDNA library. The open reading frame of the cDNA coded for an NH2-terminal signal sequence followed by a propeptide and the mature big defensin. The propeptide is linked to the mature protein through an -Arg-X-Lys/Arg-Arg- motif, the processing site for Kex2-like proteases. Northern blot analysis revealed that big defensin is expressed in all the tissues tested, suggesting that big defensin plays an important role not only in hemocytes but also in other tissues for host defense. The subcellular localization, determined by immunocytochemistry at ultrastructural level, confirmed the previous findings obtained by biochemical analysis that big defensin locates in both small and large granules in hemocytes. Big defensin is the first example to demonstrate the existence of broad tissue distribution in horseshoe crab.

Amino Acid Sequence↗