The differential role of renoguanylin in osmoregulation and apical Cl - / HCO 3 - exchange activity 1 in the posterior intestine of the Gulf toadfish (

24 The guanylin family of peptides are effective regulators of intestinal physiology in marine 25 teleosts. In the distal intestinal segments, they inhibit or reverse fluid absorption by inhibiting the 26 absorptive short-circuit current (ISC). The present findings demonstrate that mRNA from 27 guanylin (GN) and uroguanylin (UGN), as well as at least one isoform of the guanylin peptide 28 receptor, apical guanylyl cyclase-C (GC-C), was highly expressed in the intestine and rectum of 29 the Gulf toadfish (Opsanus beta). In the posterior intestine, GC-C, as well as the cystic fibrosis 30 transmembrane conductance regulator (CFTR) and basolateral Na/K/2Cl-cotransporter 31 (NKCC1), which comprise a Cl-secretory pathway, were transcriptionally upregulated in 60 ppt. 32 The present study also shows that, in intestinal tissues from Gulf toadfish held in 35 ppt, 33 renoguanylin (RGN) expectedly causes net Cl secretion, inhibits both the absorptive ISC and 34 fluid absorption, and decreases HCO3 secretion. Likewise, in intestinal tissues from Gulf 35 toadfish acclimated to 60 ppt, RGN also inhibits the absorptive ISC and fluid absorption, but to an 36 even greater extent, corresponding with the mRNA expression data. In contrast, RGN does not 37 alter Cl flux and, instead, elevates HCO3 secretion in the 60 ppt group, suggesting increased 38 apical Cl/HCO3 exchange activity by SLC26a6. Overall, these findings reinforce the hypotheses 39 that the guanylin peptide system is important for salinity acclimatization and that the secretory 40 response could facilitate the removal of solids, such as CaCO3 precipitates, from the intestine. 41