Asymmetric release of cyclic AMP from guinea-pig and rabbit gallbladder

Abstract

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 x 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.

Cyclic AMP inhibits Na+/H+ exchange at the apical membrane of Necturus gallbladder epithelium.

“…The reasons for these differences are not clear (for a discussion, see Reuss, 1984). The inhibition of salt and fluid transport produced by cAMP in several fluid-absorbing epithelia (Field, 1979 ;Frizzell et al ., 1979;Petersen et al, 1982) was attributed to inhibition of coupled NaCl entry (Frizzell et al, 1975 ;Diez de los Rios et al, 1981). In the studies of Diez de los Rios et al on Necturus gallbladder, this interpretation was based on the measurement of decreases in both a Na; and aCl ; in the absence of changes in membrane voltage.…”

Adenosine and Kidney Function

“…The ␤-blocker propranolol, IBMX, and AMPCP blocked the isoproterenol-induced increase of purines (214). Also in the isolated guinea pig gallbladder, a model of a transporting epithelium, substantial cAMP release into the extracellular space was found after stimulation with prostaglandins (265). Thus the formation of adenosine from extracellular cAMP suggests that adenosine by activation of adenosine A 1 receptors, which can be coupled to an inhibitory G i protein (see sect.…”

Cyclic AMP-induced chloride permeability in the apical membrane of Necturus gallbladder epithelium.

“…One of the most intriguing features of NaC1 absorption by mammalian and amphibian gallbladders is the mutual dependence of Na andC1 entry across the apical membrane (Cremaschi and H6nin, 1975;Frizzell et al, 1975;Reuss and Grady, 1979;Garcia-Diaz and Armstrong, 1980;Rose and Nahrwold, 1980;Ericson and Spring, 1982). This entry step is believed to be the target of cyclic adenosine-3',5 '-monophosphate (cAMP) in its inhibition of NaC1 absorption (Frizzell et al, 1975;Diez de los Rios et al, 1981;Petersen et al, 1982). Whereas NaC1 absorption is reduced by ~50% in rabbit gallbladder by cAMP (Frizzell et al, 1975), in guinea pig gallbladder, secretion of Na, K, and HCO3 is observed (Heintze et al, 1979).…”