Abstract
Renal Na+,K+-ATPase (NKA) is of great importance for the regulation ofsalt metabolism and its activity can be inhibited by several natriuretichormones. So far, the effect of antinatriuretic factors have been less wellstudied.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 forthese effects, 2) to study if insulin and the proinsulin connecting peptide(C-peptide) also stimulated NKA activity and 3) to compare the NKAresponse to NPY in PT segments of infant and adult rats.We found that NPY stimulates PT NKA via Ca-dependent signalingpathways. Stimulation was only observed at non-saturating Na+concentrations, and will therefore result in an increase of the driving forcefor transcellular Na+ transport. NPY acted synergistically with a-adrenergicreceptors (a-AR) through Ca2+ activation and antagonistically with 13-receptors (b-AR) via the inhibition of cAMP accumulation. We speculatethat 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 stimulateNKA activity and the C-peptide effect appeared to be mediated via a G-protein coupled receptor and Ca2+-dependent signaling pathway(s). Theseobservations support the concept that C-peptide acts as a peptide hormone.Each hormone tested stimulated NKA activity only when pharmacologicaldoses were tested. If, however, they were used in combination, they causedstimulation of NKA activity when physiological doses were used. Wespeculate that such dual regulation of NKA activity will provide a moresensitive system for the regulation of renal sodium handling.In infant rats, oc-adrenergic agonists and NPY failed to regulate PT NKAactivity when used alone but when used in combination, they elicited astimulatory response. The [Ca2+]i response to each agent was lesspronounced 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 ofthe infant to regulate sodium homeostasis.Key words: Norepinephrine, oc-adrenergic, beta-adrenergic, neuropeptide Y,Na+,K+-ATPase activity, C-peptide, ontogenyISBN 91-628-1941-0
