G-protein-linked serotonin receptors in mouse kidney exhibit identical properties to 5-HT1b receptors in brain.
The serotonin 1b (5-HT1b) receptor is thought to mediate both pre- and postsynaptic actions of serotonin. Until recently 5-HT1b sites were thought to be present only in rodent brain. We now report the presence of high-affinity [125I]iodocyanopindolol [( 125I] ICYP) binding sites in the mouse renal medulla with properties identical to those of brain 5-HT1b receptors. In vitro receptor autoradiography demonstrates that [125I]ICYP binding is highly localized to the outer stripe of the renal medulla. Association and dissociation kinetics, saturation analysis and competition displacement analyses indicate that renal medullary [125I]ICYP binding sites exhibit identical properties with brain 5-HT1b receptors. Incubation of renal medullary or brain membranes with guanylimidodiphosphate results in a decreased affinity of 5-HT1b sites for 5-HT and [125I]ICYP; this can be reversed by the addition of a purified mixture of G proteins (Gi/Go). Treatment of brain or kidney membranes with N-ethylmaleimide results in a decrease in 5-HT1b binding which can also be restored by reconstitution with purified G proteins. Adenylyl cyclase from renal medullary homogenates or minces can be stimulated more than 3-fold by forskolin and attenuated by 5-HT. These results indicate that mouse kidney contains high-affinity 5-HT1b receptors with identical properties to those found in brain. These are localized in the outer stripe of the renal medulla and are functionally coupled to adenylyl cyclase inhibitor (Gi) G-proteins.
Ciaranello
R D
RD
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California.
Tan
G L
GL
Dean
R
R
D000478:Alkylation; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D005033:Ethylmaleimide / Q000378:metabolism / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010869:Pindolol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D007457:Iodine Radioisotopes; D011985:Receptors, Serotonin; D005576:Colforsin; D020120:Iodocyanopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D005033:Ethylmaleimide