Summary
The adenylate cyclase stimulator forskolin enhanced both mucosal cyclic AMP levels and d-aldohexose transport in rat jejunum in vitro in a concentration-dependent manner. With mucosal cyclic AMP elevated to 400% of basal values, active d-glucose transport was at 200% of control values. Transport parameters, as determined in a three compartment model using a dual label method, indicate a) increased “uphill” glucose transport at the brush border membrane with higher intracellular accumulation, b) unchanged serosal to mucosal glucose fluxes and passive permeabilities.
Transport stimulating effects of forskolin were also present with d-galactose in the rat. In mouse jejunum active transport of d-glucose and 3-O-methylglucose was increased by forskolin 10 μmol/l.
Phlorizin inhibited d-glucose transport as well as l-glucose transport in the rat were not changed by the persisting cyclic AMP elevation induced by forskolin.
The results show a positive correlation of active intestinal hexose transport with a modest elevation of mucosal cyclic AMP.
In accordance to current models of cyclic AMP-induced changes in intestinal fluid absorption, rat jejunal net fluid transport was reduced by 40% with 20 μmol/l forskolin.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baillie TH (1981) The use of stable isotopes in pharmacological research. Pharmacol Rev 33:81–132
Beubler E, Lembeck F (1980) Inhibition by morphine of prostaglandin E1-stimulated secretion and cyclic adenosine 3′,5′-monophosphate formation in the rat jejunum in vivo. Br J Pharmacol 68:513–518
Binder HJ (1981) Colonic secretion. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven Press, New York, pp 1003–1019
Bridges RJ, Rummel W, Simon B (1983) Forskolin induced chloride secretion across the isolated mucosa of rat colon descendens. Naunyn-Schmiedeberg's Arch Pharmacol 323:355–360
Crane RK (1960) Intestinal absorption of sugars. Physiol Rev 40:789–825
Crane RK, Dorando FC (1979) On the mechanism of Na+-dependent glucose transport. Ann NY Acad Sci 339:46–55
Cuthbert AW, Spayne JA (1982) Stimulation of sodium and chloride transport in epithelia by forskolin. Br J Pharmacol 76:33–35
Diedrich DF (1965) In vitro evaluation of the relative inhibitory potency of phlorizin and its congeners. Am J Physiol 209:621–626
Goldner AM, Sarracino S, Estep JA (1977) Coupling of sodium and substrate fluxes in the intestine: galactose transport in the jejunum, In: Lauterbach FO, Kramer E (eds) Intestinal permeation. Excerpta medica Int Congress Series 391, New York, pp 282–293
Holman GD, Naftalin RJ (1975) d-Galactose accumulation in rabbit ileum: Effects of theophylline on serosal permeability. Biochim Biophys Acta 406:386–401
Holman GD, Naftalin RJ (1976) Transport of 3-O-methylglucose and β-methylglucoside by rabbit ileum. Biochim Biophys Acta 433:597–614
Hopfer U, Groseclose R (1980) The mechanism of Na+-dependent d-glucose transport. J Biol Chem 255:4453–4462
Kinzie JL, Ferrendelli JA, Alpers DH (1973) Adenosine cyclic 3′,5′,-monophosphate mediated transport of neutral and dibasic amino acids in jejunal mucosa. J Biol Chem 248:7018–7024
Kotik A, Kolinska J, Veres K, Szammer J (1965) Inhibition by phloretin and phlorizin derivatives of sugar transport in different cells. Biochem J 342:129–138
Lauterbach FO (1975) Intestinal two stage transfer of sugars and its inhibition by phlorizin. Naunyn-Schmiedeberg's Arch Pharmacol 287 (Suppl): R28
Lemmer B, Lang PH, Bissinger H (1984) Indications for circadian variations in cyclic AMP contents, adenylate cyclase and phosphodiesterase activities in rat heart ventricles. Naunyn-Schmiedeberg's Arch Pharmacol 325 (Suppl): R32
Muller HJ, Baer HP (1983) Relaxant effects of forskolin in smooth muscle. Role of cyclic AMP. Naunyn-Schmiedeberg's Arch Pharmacol 322:78–82
Murer H, Burckhardt G (1983) Membrane transport of anions across epithelia of mammalian small intestine and kidney tubule. Rev Physiol Biochem Pharmacol 96:1–41
Naftalin RJ, Curran PF (1974) Galactose transport in rabbit ileum. J Membr Biol 16:257–258
Naftalin RJ, Holman GD (1974) The role of Na+ as a determinant of the asymmetric permeability of rabbit ileal brush border to d-galactose. Biochim Biophys Acta 373:453–470
Reymann A, Braun W, Dräger J (1983) Effects of DDT and Dieldrin on intestinal glucose transport and brush border hydrolases. A comparison with phenobarbital and methylcholanthrene. Biochem Pharmacol 32:1759–1763
Schultz SG (1979) Transport across the small intestine. In: Giebisch G, Tosteson DC, Ussing HH (eds) Membrane transport in biology, vol IVb. Springer, Berlin Heidelberg New York, pp 749–789
Seamon KB, Padgett W, Daly JW (1981) Forskolin: A unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci USA 78:3363–3367
Stevenson NR, Fierstein JS (1976) Circadian rythms of intestinal sucrase and glucose transport: Cued by time of feeding. Am J Physiol 230:731–735
Trendelenburg U, Stefano FJE, Grohmann M (1983) The isotope effect of tritium in 3H-noradrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 323:128–140
Tovey KC, Oldham KG, Whelan JAM (1974) A simple direct assay for cyclic AMP in plasma and other biological samples using an improved competitive protein binding technique. Clin Chim Acta 56:221–234
Ullrich KJ (1979) Sugar, amino acid and Na+-cotransport in the proximal tubule. Annu Rev Physiol 41:181–195
Winne D, Görig H (1982) Appearance of 14C-polyethyleneglycole 4000 in intestinal venous blood: Influence of osmolarity and laxatives, effect on net water flux determination. Naunyn-Schmiedeberg's Arch Pharmacol 321:149–156
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Reymann, A., Braun, W., Bergheim, M. et al. Forskolin-induced elevation of rat jejunal cyclic AMP levels and stimulation of active glucose transport in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 317–323 (1985). https://doi.org/10.1007/BF00515560
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00515560