AMP-activated protein kinase and adenosine are both metabolic modulators that regulate chloride secretion in the shark rectal gland (Squalus acanthias)

摘要

The production of endogenous adenosine during secretagogue stimulation of CFTR leads to feedback inhibition limiting further chloride secretion in the rectal gland of the dogfish shark (Squalus acanthias). In the present study, we examined the role of AMP-kinase (AMPK) as an energy sensor also modulating chloride secretion through CFTR. We found that glands perfused with forskolin and isobutylmethyfxanthine (F + I), potent stimulators of chloride secretion in this ancient model, caused significant phosphor-ylation of the catalytic subunit Thr172 of AMPK. These findings indicate that AMPK is activated during energy-requiring stimulated chloride secretion. In molecular studies, we confirmed that the activating Thr172 site is indeed present in the a-catalytic subunit of AMPK in this ancient gland, which reveals striking homology to AMPKa subunits sequenced in other vertebrates.