Characteristics of endothelin receptors in the central nervous system of spontaneously hypertensive rats.
The binding of [125I]sarafotoxin 6b (SRT 6b) and [125I]endothelin-1 (ET-1) to endothelin (ET) receptors of neuronal membranes prepared, from regions of the brain and spinal cord of 8 week-old, spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. Spontaneously hypertensive rats had significantly higher blood pressure as compared to WKY rats. Heart rate was similar in SHR and WKY rats. [125I]SRT 6b and [125I]ET-1 bound to the membranes of the cerebral cortex, hypothalamus, ventrolateral medulla, dorsomedial medulla and spinal cord at a single, high affinity site. The Kd and Bmax values of the binding of [125I]SRT 6b were found to be similar to binding of [125I]ET-1 in all the regions. The concentration-dependent inhibition of binding of [125I]ET-1 by unlabeled ET-1, in spinal cord membranes showed an IC50 value of 2.66 +/- 0.59 nM and a Ki value of 2.35 +/- 0.52 nM in WKY rats and an IC50 value of 2.82 +/- 0.76 nM and a Ki value of 2.43 +/- 0.70 nM in SHR rats. On the other hand, the concentration-dependent inhibition of the binding of [125I]SRT 6b by unlabeled ET-1, in spinal cord membranes showed an IC50 value of 10.31 +/- 1.82 pM and a Ki value of 8.44 +/- 1.41 pM in WKY rats, while SHR rats showed an IC50 value of 10.28 +/- 1.94 pM and a Ki value of 8.89 +/- 2.00 pM. The binding of [125I]SRT 6b and [125I]ET-1 in the cerebral cortex, dorsomedial medulla and spinal cord membranes was found to be similar in SHR and WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS) [corrected]
Gulati
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Department of Pharmacodynamics (m/c 865), University of Illinois, Chicago 60612.
Rebello
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin; D014757:Viper Venoms / Q000378:metabolism
D016232:Endothelins; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6