Activities of seasonably variable caerulein and rothein skin peptides from the tree frogs Litoria splendida and Litoria rothii

Two species of tree frog of the genus Litoria, namely L. splendida and L. rothii have been reported to change the compositions of their host-defence skin peptide profiles in summer and winter. L. splendida produces the potent smooth muscle active caerulein [pEQDY(SO3H)TGWMDF-NH2] in summer, but in winter much of the caerulein is hydrolysed to the less active desulfated form; in addition, caerulein 1.2 [pEQDY(SO3H)TGWFDF-NH2] (which has only some 50% of the smooth muscle activity of caerulein) is released and acts via CCK2R. In contrast, Litoria rothii shows a most unexpected seasonal change of peptides. In summer it exudes caerulein together with a range of potent caerin antimicrobials and nNOS active peptides. In winter, none of the antibiotic or nNOS active caerin peptides are expressed. The major peptides produced by the skin glands in winter are caerulein 1.2 and rothein 1 (SVSNIPESIGF-OH). Like L. splendida, L. rothii has reduced the smooth muscle potency of caerulein by replacing it with caerulein 1.2. Rothein 1 is a lymphocyte proliferator acting via CCK2R. Activity testing and 2D NMR spectra of rothein 1 and some synthetic modifications indicate that both hydrophobic and hydrophilic interactions between rothein 1 and CCK2R are important.