Abstract
Renal Na+,K+-ATPase (NKA) is of great importance for the regulation of salt metabolism and its activity can be inhibited by several natriuretic hormones. So far, the effect of antinatriuretic factors have been less well studied. The aims of this project were 1) to study whether proximal tubule (PT)NKA can be stimulated by the renal neurotransmitters, norepinephrine (NE) and neuropeptide Y (NPY), and if so, to identify the signalling pathways for these effects, 2) to study if insulin and the proinsulin connecting peptide (C-peptide) also stimulated NKA activity and 3) to compare the NKA response to NPY in PT segments of infant and adult rats. We found that NPY stimulates PT NKA via Ca-dependent signaling pathways.
Stimulation was only observed at non-saturating Na+ concentrations, and will therefore result in an increase of the driving force for transcellular Na+ transport. NPY acted synergistically with a-adrenergic receptors (a-AR) through Ca2+ activation and antagonistically with 13-receptors (b-AR) via the inhibition of cAMP accumulation. We speculate that NPY shifts the balance between a- and b-AR in such a way that the b-mediated effect becomes dominant. Both insulin and C-peptide stimulate NKA activity and the C-peptide effect appeared to be mediated via a G-protein coupled receptor and Ca2+-dependent signaling pathway(s).
These observations support the concept that C-peptide acts as a peptide hormone. Each hormone tested stimulated NKA activity only when pharmacological doses were tested. If, however, they were used in combination, they caused stimulation of NKA activity when physiological doses were used. We speculate that such dual regulation of NKA activity will provide a more sensitive system for the regulation of renal sodium handling. In infant rats, oc-adrenergic agonists and NPY failed to regulate PT NKA activity when used alone but when used in combination, they elicited a stimulatory response. The [Ca2+]i response to each agent was less pronounced in infant than in adult rats. We speculate that the Ca2+-dependent intracellular signaling systems in the kidney develop postnatally, and that immaturity of those systems may contribute to the poor capacity of the infant to regulate sodium homeostasis.
