Cyclic nucleotide-mediated effects of ANF and VIP on flounder intestinal ion transport

The purpose of this study was to compare the effects of atriopeptin III (AP-III), vasoactive intestinal peptide (VIP), and ionomycin on Na and Cl influx and to correlate changes in transport with effects on intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 5'-cyclic monophosphate (cGMP) content of the tissue. In addition, the question of whether AP-III inhibits ion transport directly by acting on enterocyte receptors for AP-III or indirectly by stimulation of enteric nerves in the submucosa was also addressed. The results showed that AP-III, ionomycin, and bumetanide all inhibited the initial rate of Na and Cl influx, suggesting that they directly block Na-K-2Cl cotransport activity. VIP had no effect on unidirectional influx of Na and Cl. AP-III caused a fourfold increase in intracellular [cGMP] without any significant effect on [cAMP]. VIP stimulated [cAMP] by fourfold but had no effect on [cAMP]. Ionomycin had no effect on either [cAMP] or [cGMP]. Inhibition of transport by AP-III could not be blocked by tetrodotoxin (TTX), indicating that enteric nerves in the submucosa are not directly involved in mediating the effects of AP-III on epithelial ion transport. The observation that two classes of neuronal depolarizing agents (veratrine and scorpion venom) cause TTX-sensitive inhibition of basal ion transport establishes that NaCl absorption in flounder intestine is subject to regulation by enteric nerves located in the submucosa.