J Comp Physiol (1982) 146:27-34 Journal of Comparative Physiology. B Springer-Verlag 1982 Effects of Epinephrine, Glucagon and Vasoactive Intestinal Polypeptide on Chloride Secretion by Teleost Opercular Membrane J. Kevin Foskett, Guylaine M. Hubbard, Terry E. Machen*, and Howard A. Bern Departments of Zoology and Physiology-Anatomy*, and Cancer Research Laboratory, University of California, Berkeley, California 94720, USA Accepted October 26, 1981 Summary. The effects of epinephrine, glucagon and vasoactive intestinal polypeptide on chloride secretion by chloride cell-containing isolated opercular mem- branes from the seawater-adapted euryhaline teleost, the tilapia Sarotherodon mossambicus, have been ex- amined. Epinephrine inhibits chloride secretion, mea- sured as the short-circuit current (Iso), via e-receptors, in a dose-dependent fashion. The minimum effective dose is 10 -9 M, EDso equals 2 x 10 -7 M and maxi- mal inhibition at 10-SM is nearly 80%. Inhibition of phosphodiesterase by isobutylmethylxanthine (IBMX; 10 -4 M), does not alter Isc in untreated tis- sues, but it completely reverses the epinephrine inhibi- tion of Isc, suggesting that hormones which modulate cAMP in chloride cells may alter chloride secretion. Glucagon and vasoactive intestinal polypeptide also stimulate Isc in epinephrine-inhibited tissues, an effect potentiated by IBMX. The effect of glucagon is dose- dependent with a minimum effective dose of 10-9 M, EDs0 equal to 8 x 10 -8 M and a maximum stimula- tion of 72% at 10 -5 M. Analysis of the effects of epinephrine and IBMX on Isc and tissue conductance suggests that these agents act antagonistically on a nonconductive trans- port mechanism. It is proposed that IBMX and hor- mones which increase intracellular cAMP levels sti- mulate chloride secretion in epinephrine-inhibited tis- sues by stimulating a neutral sodium chloride cellular entry-step mechanism. Introduction The isolated opercular membrane from the seawater- adapted tilapia, Sarotherodon mossambicus, actively secretes chloride at a rate equal to the short-circuit Abbreviations." ED50 effective dose causing half-maximal inhibition or stimulation ; IBMX isobutylmethylxanthine; VIP vasoactive in- testinal polypeptide current (Foskett et al. 1981). The many morphologi- cal and physiological parallels between this tissue, the Fundulus heteroclitus opercular membrane and the Gillichthys mirabilis skin on one hand, and the bran- chial epithelium on the other, suggest that these tis- sues are good models for study of branchial salt- extrusion mechanisms. These flat-sheet epithelia pos- sess chloride cells which have been demonstrated to be responsible for chloride secretion by the tilapia opercular membrane (Foskett and Scheffey 1982) and which are morphologically similar to those of the branchial epithelium (Karnaky and Kinter 1977; Marshall and Nishioka 1980; Foskett et al. 1981). Further, these tissues respond to seawater adaptation (Foskett et al. 1981), ion transport inhibitors (Kar- naky et al. 1977; Marshall 1977; Degnan et al. 1977; Degnan and Zadunaisky 1979; Mayer-Gostan and Maetz 1980; Foskett et al. 1981) and fast-acting (Deg- nan etal. 1977; Marshall and Bern 1980; Mayer- Gostan and Maetz 1980; Foskett et al. 1981) and long-term (Mayer-Gostan and Zadunaisky 1978; Marshall and Bern 1980; Foskett et al. 1982) hormonal stimuli in fashions analogous to the branchial re- sponses (Maetz and Bornancin 1975; Karnaky 1980). Use of these isolated preparations is especially advantageous for examining the effects of fast-acting hormones on salt-transport mechanisms since, unlike the branchial epithelium, they can be studied free of the possible hemodynamic and other effects of these agents. Chloride secretion by chloride cells ap- pears to be under multiple hormonal control. Thus, epinephrine (Degnan et al. 1977; Marshall and Bern 1980; Mayer-Gostan and Maetz 1980; Foskett et al. 1981), somatostatin (Foskett and Hubbard 1981) and the caudal neurosecretory peptide urotensin II (Mar- shall and Bern 1979, 1981 ; Loretz et al. 1981) inhibit chloride secretion and urotensin I (Marshall and Bern 1981) and phosphodiesterase inhibitors (Degnan et al. 1977; Marshall and Bern 1979, 1981; Foskett et al. 1982) stimulate it in these tissues. 0174-1578/82/0146/0027/$01.60