Abstract
The perfusion of rat small intestinal lumen with epinephrine (0.1 mM) resulted in a significant increase in the amount of benzylpenicillin (BP) transported from the mucosal to the serosal side. In this study, the perfusion of the lumen with phenylephrine, clonidine, dobutamine, or salbutamol had no effect on BP transport. However, the combinations of phenylephrine and isoproterenol, clonidine and isoproterenol, and phenylephrine and salbutamol increased the BP transport to a similar extent as that observed with epinephrine alone. Tolazolin or propranolol inhibited the epinephrine-induced increase in BP transport. An increase in the intracellular concentration of cAMP in conjunction with specific activation of either α1- or α2-adrenoceptors induced an increase in BP transport similar to that observed in response to epinephrine alone. Staurosporine orN-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide abolished the epinephrine-induced increase in BP transport. Peptides or either zwitterionic or anionic cephalosporins also blocked the effect of epinephrine on BP transport. The extent of BP uptake into brush border or basolateral membrane vesicles prepared from epinephrine-perfused intestinal loops was markedly greater than that into vesicles prepared from control loops. The perfusion of intestinal lumen with carbonyl cyanide p-trifluoromethoxy phenylhydrazone, amiloride, or ouabain inhibited epinephrine-induced BP transport. These results indicate that the interaction of epinephrine with both β2-adrenoceptors and either α1- or α2-adrenoceptors markedly stimulates the BP transport, an effect likely mediated by the enhancement of the function in the brush border membrane of intestinal epithelial cells coupled with the generation of an H+ gradient.
Footnotes
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Send reprint requests to: Dr. Yasuko Ishikawa, Department of Pharmacology, Tokushima University School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. E-mail:isikawa{at}dent.tokushima-u.ac.jp
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↵1 This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.
- Abbreviations:
- BBM
- brush border membrane
- BP
- benzylpenicillin
- BLM
- basolateral membrane
- FCCP
- carbonyl cyanidep-trifluoromethoxy phenylhydrazone
- H-8
- N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride
- PKA
- cyclic AMP-dependent protein kinase
- Mes
- 2-(N-morpholino)ethanesulfonic acid
- Received August 10, 1999.
- Accepted November 22, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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