Prostaglandin regulation of H⁺ secretion in amphibian epithelia

The role of prostaglandins in regulating H⁺ excretion in amphibian epithelia was investigated. The abdominal skin of the southern leopard frog Rana pipiens and the urinary bladder of the toad Bufo marinus were used to measure proton excretion across their mucosal surface. Prostaglandin F(2α) (PGF(2α)) produced a dose-dependent inhibition of H⁺ excretion across the frog skin. Frogs pretreated with ibuprofen (30 mg·kg^-1·day^-1 for 3 days) showed an enhanced proton excretion similar to that observed when frogs are placed in chronic metabolic acidosis. The number of mitochondria-rich cells, the cells responsible for proton excretion, was also increased in frog skins after chronic metabolic acidosis or ibuprofen treatment. Mezerein and the phorbol ester 4β-phorbol 12-myristate 13-acetate (4β-PMA), activators of protein kinase C (PCK), decreased H⁺ excretion in frog skin, whereas the inactive phorbol 4α-PMA was without an effect. The inhibition of proton excretion was similar to that observed with PGF(2α) and suggested that the effects of PGF(2α) and activation of PKC were mediated through a common pathway. Frogs pretreated with ibuprofen not only had an enhanced proton excretion rate but also had a decrease in cytosolic PKC activity. In another amphibian tissue, the toad urinary bladder, PGE₂ inhibited proton excretion at low doses but enhanced H⁺ excretion at higher doses. Toads maintained under chronic metabolic acidosis had enhanced proton excretion rates and also had a threefold increase in cellular PGE₂ concentration, which was consistent with the observation that PGE₂ enhanced proton excretion at high doses. Collectively, these observations suggest that prostaglandins and activation of PKC may play a role in regulating basal H⁺ excretion in amphibian epithelia.