Abstract:
:1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions between RMIC and vasoactive peptides are important in the regulation of renal function. 2. We aimed to localize the BK B2 receptor binding site to RMIC in vivo and to also demonstrate that these receptors are biologically active in vitro. 3. The present study demonstrates BK B2 binding sites on RMIC of the inner stripe of the outer medulla and the inner medulla of the rat kidney in vivo. 4. We further demonstrate that the BK B2 radioligand [125I]-HPP-Hoe140 specifically bound to rat RMIC in vitro. In addition, reverse transcription-polymerase chain reaction detected the mRNA for the BK B2 receptor subtype in cell extracts. 5. For RMIC in vitro, cAMP levels were increased at 1 min and cGMP levels were increased at 2 min after treatment with 10(-10) and 10(-7) mol/L BK, respectively. Inositol 1,4,5-trisphosphate was increased at 10 s treatment with both 10(-6) and 10(-7) mol/L BK. 6. For RMIC in vitro, BK induced an increase in cell proliferation ([3H]-thymidine incorporation) and an increase in extracellular matrix synthesis (ECM; trans-[35S] incorporation), both effects mediated by BK B2 receptors. 7. We conclude that BK B2 receptors are present on RMIC both in vivo and in vitro. These receptors are coupled to intracellular second messenger systems and, in vitro, their stimulation results in cellular proliferation and synthesis of ECM.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Dean R,Maric C,Aldred GP,Casley D,Zhuo J,Harris P,Alcorn D,Mendelsohn FAdoi
10.1046/j.1440-1681.1999.02981.xkeywords:
subject
Has Abstractpub_date
1999-01-01 00:00:00pages
48-55issue
1eissn
0305-1870issn
1440-1681journal_volume
26pub_type
杂志文章abstract::1. Sodium (Na) depletion, due to uncompensated loss of parotid saliva, reduces the pressor responsiveness to angiotensin II (AII) in intact conscious sheep. 2. Inhibition of prostaglandin synthesis by indomethacin restored AII pressor responsiveness in Na-deplete sheep. 3. Indomethacin infusion also increased the pres...
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