Internalization of human rhinovirus 14 into HeLa and ICAM-1-transfected BHK cells.

Virus adsorption and uptake of human rhinovirus 14 (HRV14) were studied with HeLa cells and baby hamster kidney (BHK) cells which were transfected with the HRV14 receptor intercellular adhesion molecule-1 (ICAM-1). Transmission electron microscopy of HeLa cells revealed that HRV14 was internalized via clathrin-coated pits and -coated vesicles. A minority of virus particles also used uncoated vesicles for entry. The internalization showed the characteristics of receptor-mediated endocytosis. Presence of the carboxylic ionophore monensin inhibited viral uncoating, indicating a pH-dependent entry mechanism. The expression of ICAM-1 on the surface of the ICAM-1 transfected baby hamster kidney cells (BHK-ICAM cells) allowed extensive virus adsorption and internalization through membrane channels. Virus particles were lined up in these channels like pearls on a string, but did not induce a productive infection. Although ICAM-1 was expressed to the same degree on BHK-ICAM and HeLa cells, HRV14 induced neither viral protein and RNA syntheses nor infectious virus progeny in BHK-ICAM cells. ICAM-1 on the transfected BHK cells was a functional active receptor as it rendered these cells permissive to coxsackievirus A21. These results suggest that HRV14 uptake into BHK-ICAM cells is blocked directly in or shortly after its final step of internalization, the uncoating. Our findings underline that the receptor ICAM-1 determines virus uptake into cells, however, is not sufficient to confer susceptibility of BHK cells to HRV14 infection.

[Metoclopramide antagonizes dopamine-induced inhibition of lower esophageal sphincter pressure in the awake beagle]. / Metoclopramid (MCP) antagonisiert die Dopamin (DOP)-induzierte Hemmung des unteren Osophagussphinkterdruckes (UOSD) am wachen Beagle.

Different contradictory results, even in the same species of the DOP-effect on LESP have been reported. The aim of the present studies was to evaluate the effect of DOP on LES in purebread male beagles and whether in could be antagonised by the DOP-antagonist MCP. The LESP in beagles is sensitive to dopamine (DOP) and its "antagonist", metoclopramide (MCP). MCP raised the inhibited LESP after DOP-infusion in vivo, while it failed to change DOP-induced relaxation of opossum LES in vitro [1]. Data obtained after monotherapie with MCP did not exceed LESP-response to MCP after DOP-pretreatment. DOP applied as background counter-inhibition could be used to correct interdigestive phasic changements of LESP in order to reach a stable starting-point to investigate the action of LESP-stimulating compounds pharmacomanometrically. Due to DOP reflux-facilitating side effect via its decrease of LESP, large doses of DOP, as used in the intensiv care unit, should be administered together with sphincter-strengthening agents or antacid compounds.

Effects of exepanol-HCl, metoclopramide and domperidone on the lower esophageal sphincter of dogs.

The actions of rac. 3,5-cis-2,3,4,5-tetrahydro-3-methylamino-1-benzoxepine-5-ol hydrochloride (prop. INN exepanol-HCl, KC 2450), metoclopramide and domperidone on the resting pressure of the lower esophageal sphincter (LES) were studied in anesthetized and conscious beagle dogs using pull-through manometrical methods. Exepanol-HCl proved to enhance the LES pressure (LESP) significantly both in anesthetized and conscious dogs. The action of domperidone which was used as reference compound in the anesthetized dog experiments was less pronounced. In conscious dogs the actions of exepanol-HCl and metoclopramide were comparable. Domperidone was not active in this test.