Rat renomedullary interstitial cells possess bradykinin B-2 receptors in vivo and in vitro

1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoa ctive peptides, including atrial natriuretic peptide, endothelin, angiotens in 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 B-2 receptor binding site to RMIC in vivo an d to also demonstrate that these receptors are biologically active in vitro . 3. The present study demonstrates BK B-2 binding sites on RMIC of the inner stripe of the outer medulla and the inner medulla of the rat kidney in viv o. 4. We further demonstrate that the BK B-2 radioligand [I-125]-HPP-Hoe140 sp ecifically bound to rat RMIC in vitro. In addition, reverse transcription-p olymerase chain reaction detected the mRNA for the BK B-2 receptor subtype in cell extracts. 5. For RMIC in vitro, cAMP levels were increased at 1 min and cGMP levels w ere increased at 2 min after treatment with 10(-10) and 10(-7) mol/L BK, re spectively. Inositol 1,4,5-trisphosphate was increased at 10 s treatment wi th both 10(-6) and 10-7 mol/L BK. 6. For RMIC in vitro, BK induced an increase in cell proliferation ([H-3]-t hymidine incorporation) and an increase in extracellular matrix synthesis ( ECM; trans-[S-35] incorporation), both effects mediated by BK B-2 receptors , 7. We conclude that BK B-2 receptors are present on RMIC both in vivo and in vitro. These receptors are coupled to intracellular second messenger sy stems and, in vitro, their stimulation results in cellular proliferation an d synthesis of ECM.