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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 318 (1982), S. 358-362 
    ISSN: 1432-1912
    Keywords: Gallbladder ; Prostaglandins ; cAMP Release ; Fluid secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The release of cyclic adenosine 3′:5′-monophosphate (cAMP) from guinea-pig and rabbit gallbladder was investigated in vitro. Serosal addition of prostaglandin E1 (PGE1) to luminally perfused guinea-pig gallbladders caused a concentration-dependent efflux of cAMP to the mucosal side, the threshold concentration of PGE1 being 10−7 M. The efflux of cAMP to the serosal side was 7-fold lower. A mucosal sidedness of cAMP release was also observed in stripped preparations of rabbit gallbladder mucosa mounted between two half chambers. No cAMP was found in the solutions bathing the serosal layers isolated from rabbit gallbladders. Fluid secretion was observed at 10−7 M PGE1, an effect mimicked by serosal, but not mucosal application of cAMP (3.3×10−3 M). This is taken to indicate that the basolateral membrane is more easily permeated by cAMP than the apical membrane, since cAMP is believed to exerts its physiological effects from inside the cell. It is concluded that preferential release of cAMP to the mucosal side is not due to a higher permeability of the brush border membrane but rather represents an as yet undefined transport process which may be of importance for the regulation of excessive intracellular cAMP levels.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Transport regulation ; VIP ; VIP antagonist ; Histamine ; Noradrenaline ; Somatostatin ; Cl− channel blocker ; TMB 8
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In guinea-pig gallbladder epithelium, cAMP converts electroneutral HCO inf3 sup− secretion into an electrogenic process. The effects of blood side Ba2+ (5 mmol/l) on HCO inf3 sup− tranport were investigated in vitro, using pH-stat and voltage clamp techniques to determine unidirectional fluxes of HCO inf3 sup− and transepithelial electrical characteristics. Serosal, not mucosal addition of Ba2+ elevated short-circuit current (Isc), transepithelial potential difference, and tissue conductance; it inhibited the absorptive HCO inf3 sup− flux while leaving the secretory flux unchanged. The Isc effect of Ba2+ was inhibited or prevented by tetrodotoxin; D- and Lrpropranolol; the Cl− channel blocker 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; the intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester; noradrenaline, by a yohimbine-sensitive action; somatostatin; HCO inf3 sup− -free solutions. Thus Ba2+ appeared to release a neurotransmitter that gives rise to CAMP synthesis sufficcient to turn part of electroneutral HCO inf3 sup− secretion electrogenic. In a search for the involved signalling pathways, the H1-receptor antagonist, cetirizine, largely and hexamethonium, atropine, atenolol, indomethacin, and trifluoperazine entirely failed to antagonize the Isc effect of Ba2+. Similarly, carbachol, dobutamine, salbutamol, and serotonin were unable to mimick the action of Ba2+ and Isc effects of histamine were small and short-lived. By contrast, vasoactive intestinal peptide (VIP; 3 × 10−7 mol/l) completely transformed HCO inf3 sup− secretion into an electrogenic process. The VIP receptor antagonist (4Cl-dPhe6, Leu17)VIP, delayed and reduced the Isc responses to Ba2+ and VIP. As guinea-pig gallbladder epithelial cells possess cAMP-coupled VIP receptors close to VIPergic neurons, Ba2+ is likely to act by releasing VIP from neural terminals.
    Type of Medium: Electronic Resource
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