REGULATION OF OSMOTIC WATER PERMEABILITY DURING DIFFERENTIATION OF INNER MEDULLARY COLLECTING DUCT

Urinary osmotic concentration capacity during renal ontogeny is subject to changes of medullary cytoarchitecture and of segmental epithelial transport characteristics. Osmotic equilibrium between interstitial and tubular fluid of the terminal nephron segment in response to vasopressin is an absolute essential of maximal urinary osmotic concentration. The regulation of osmotic water permeability (P(f)) in this terminal epithelial segment during ontogenetic differentiation has not been documented. The inner medullary collecting duct (IMCD), the terminal 40% of total segmental length, was dissected at two stages of postnatal ontogenetic differentiation from immature (days 7-15) and from mature (days 33-37) rat kidneys and perfused in vitro. P(f) (mu-m/s) was measured (bath hyperosmotic) in the absence and presence of arginine vasopressin (AVP, 230 pM). Basal P(f) was 32.3 +/- 4.03 (n = 26) in the immature IMCD (IMCD(i)) and 111.5 +/- 20.6 (n = 15) in the mature segment (IMCD(m)). AVP increased P(f) in IMCD(i)) from 46.4 +/- 10.5 to 102 +/- 25.7-mu-m/s, whereas in IMCD(m) the AVP-dependent change of P(f) was from 104.2 +/- 41.2 to 693 +/- 176-mu-m/s. AVP (2,300 pM) did not further increase P(f) in IMCD(i). Forskolin (50-mu-M) changed P(f) in IMCD(i) from 34.9 +/- 6.3 to 104.1 +/- 16-mu-m/s; the corresponding change in IMCD(m) was from 150 +/- 32 to 985.8 +/- 133-mu-m/s. An analogue of adenosine 3',5'-cyclic monophosphate (cAMP; 10(-3) M) increased P(f) in IMCD(i) from 35.5 +/- 11.4 to 138.5 +/- 32.6 and in IMCD(m) from 79.6 +/- 32.3 to 702.2 +/- 283-mu-m/s. The results indicate that the vasopressin-dependent P(f) in IMCD is subject to differentiation processes within the peptide hormone signal system. Forskolin and cAMP effects on P(f) suggest that the initial transduction steps are expressed at low activity levels without an apparent defect during inner medullary epithelial differentiation.