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Identification of agonists of duodenal alkaline secretion
Author(s) -
GARNER A.,
HEYLINGS J. R.,
HAMPSON S. E.,
STANIER A. M.
Publication year - 1990
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.1990.tb01479.x
Subject(s) - duodenum , medicine , endocrinology , forskolin , secretion , in vivo , histamine , alkaline phosphatase , prostaglandin e2 , pharmacology , chemistry , biology , biochemistry , enzyme , microbiology and biotechnology , stimulation
. This report describes approaches for accurate determination of the comparative activities of stimulants of duodenal alkaline secretion. We screened about 200 standard pharmacological agents using a bullfrog‐isolated mucosal preparation in order to characterize fully the mechanisms of duodenal alkaline secretion. A variety of eicosanoids, phosphodiesterase (PDE) inhibitors, adrenoreceptor agonists and benzodiazepines, together with forskolin, 6‐hydroxydopamine, 2‐chloroadenosine, dipyridamole, dihydropyridazinone and testosterone, caused a reproducible increase in the metabolism‐dependent component of duodenal alkaline secretion. Prostaglandin E 2 (ED 50 of 0.02 μg ml −1 in vitro ) was the most potent and efficacious stimulant in the isolated mucosa and in the perfused cat duodenum in vivo . In the isolated duodenum, the predominant mechanism for stimulating alkaline secretion appears to be via elevation of intracellular cAMP levels, but in vivo indirect effects, for example on mucosal blood flow, may determine the overall influence of agents on duodenal alkalinization.