Conversion of sodium channels to a form sensitive to cyclic AMP by component(s) from red cells

Abstract

1Sodium transport has been measured in the isolated epithelium from colons of male SpragueDawley rats. 2 Sodium transport in colons was induced by pretreating the animals with dexamethasone (6 mg kg-) which caused the appearance of an amiloride-sensitive short circuit current within a few hours. 3 Forskolin, a diterpene, which activates adenylate cyclase, was found to increase the cyclic adenosine monophosphate (cyclic AMP) content of rat colons and also to increase short circuit current at the same time. However, measurements of chloride and sodium fluxes across the epithelium indicated that forskolin activates chloride secretion but has no effect on sodium transport.4 In confirmation of (3) it was found that the amiloride-sensitive short circuit current was unchanged after the short circuit current had been increased by forskolin under a variety of conditions. 5The behaviour of the mammalian colon as indicated in (3) and (4) is unlike that of amphibian sodium transporting epithelia. It is shown that in toad urinary bladder forskolin increases amiloridesensitive short circuit current. 6 Procedures were investigated which might make sodium transport in the mammalian colon sensitive to cyclic AMP. Exposing the apical surface to sonicated suspensions of nucleated red cells (frog, toad and duck), followed by washing, gave preparations with amiloride-sensitive short circuit currents which were increased by forskolin or dibutyryl cyclic AMP. 7 It would appear that the sodium channel in the mammalian colon, unlike that of amphibian tissues, has lost the ability to have its properties modified by cyclic AMP. Incubation of colons with sonicated suspensions of nucleated red cells apparently modifies the tissues such that sodium transport across the tissue becomes sensitive to the nucleotide.

The Effect of cAMP on Electrogenic Na+ Absorption in the Rat Distal Colon.

“…In the rat colon mounted in Ussing chambers, forskolin is reported to have no effect on the amiloride-sensitive I sc and 22 Na ϩ absorption under normal conditions, but to enhance the amiloride-sensitive I sc after the tissue was exposed to sonicated suspensions of nucleated cells [7]. The reason for the discrepancy between these results and our own is not clear.…”

“…In contrast, cAMP has hardly any effect on 22 Na ϩ absorption in the rabbit colon [6]. In the rat colon, forskolin, an adenylate cyclase activator, has no effect on the amiloride-sensitive I sc under normal conditions, but it can enhance the amiloride-sensitive I sc after the tissue is exposed to sonicated suspensions of nucleated cells [7]. Finally, cAMP and isoproterenol cause, at least initially, a decrease in the amiloride-sensitive I sc in the guinea pig and human colon [8,9].…”

Role of calcium ions in kinin‐induced chloride secretion

“…Forskolin activates adenylate cyclase by a direct effect on the catalytic subunit (Seamon et al, 1981), while IBMX prevents the degradation of cyclic nucleotides. Both agents can increase the cyclic AMP content of the rat colon epithelium (Cuthbert & Spayne, 1983). Thus both may affect chloride secretion via cyclic AMP, a well known activator of electrogenic chloride secretion in epithelia of the alimentary tract (Field, 1971;Nellans etal., 1974;Frizzell & Heintze, 1979;Smith et al, 1982).…”

“…Forskolin activates the catalytic subunit of adenylate cyclase (Seamon et al, 1981) and was used to increase intracellular cyclic AMP in the colon directly (Cuthbert & Spayne, 1983). A comparison of the effects of calcium removal on responses to forskolin and to kallidin in a paired preparation is shown in Figure 4.…”

“…To mimic more closely the situation in the rabbit, rats were given a single intraperitoneal injection of dexamethasone (6 mg kg-1) and colon preparations prepared 17 h later. These preparations show electrogenic sodium absorption which is sensitive to amiloride (Cuthbert & Spayne, 1983). However, A23187 produced similar small responses in these tissues to those of normal colons.…”