Effects of PTH, calcitonin, and cAMP on calcium transport in rabbit distal nephron segments.
Distal nephron segments are heterogenous with respect to adenylate cyclase responses to stimulation with parathyroid hormone (PTH) or calcitonin (CT). We examined effects of these hormones and of 8-(p-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPTcAMP) on net Ca absorption (Jnet Ca2+, pmol.min-1.mm-1) in rabbit distal nephron segments by in vitro microperfusion technique. We studied three segments, including distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD). PTH (1 nM) in bath significantly increased Jnet Ca2+ from 2.28 +/- 0.35 to 9.44 +/- 1.13 in CNT, but did not affect Jnet Ca2+ in DCT or CCD. CT (1 nM) in bath significantly increased Jnet Ca2+ from 1.58 +/- 0.29 to 4.45 +/- 1.01 in DCT, whereas it did not affect Jnet Ca2+ either in CNT or in CCD. CPTcAMP (30 microM) in bath significantly increased Jnet Ca2+ from 2.29 +/- 0.42 to 3.97 +/- 0.43 in DCT and from 2.43 +/- 0.18 to 5.83 +/- 0.37 in CNT, but it did not affect Jnet Ca2+ in CCD. When Na+ was removed from bathing fluid or when 0.1 mM ouabain was added to bath, Jnet Ca2+ in both DCT and CNT significantly decreased. Furthermore, stimulatory effects of PTH and CT on Ca2+ absorption in the respective segments were abolished under these conditions. These results suggest that PTH and CT increase Ca2+ absorption in CNT and DCT, respectively, through cAMP-mediated mechanisms. Presence of a basolateral Na(+)-Ca2+ exchange process seems to be a prerequisite for effects of these hormones. However, exact intracellular mechanisms remain uncertain.
Shionogi Research Laboratories, Shinogi & Company, Osaka, Japan.
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Shimizu
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Yoshitomi
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Nakamura
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Imai
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D007546:Isoquinolines; D010281:Parathyroid Hormone; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D010042:Ouabain; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D002116:Calcitonin; D012964:Sodium; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine