Dopamine D1 and D2 receptors in the caudate nucleus of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.
A series of studies was carried out to characterize the binding properties of dopamine D1 and D2 receptors in membrane homogenates of the caudate nucleus of spontaneously hypertensive rats (SHR). Binding in SHR was studied at the age of 4 weeks when the rats were still in the prehypertensive phase, and at the age of 8 weeks, during the phase in which blood pressure is increasing dramatically; age-matched normotensive Wistar-Kyoto rats (WKY) were used as controls. Binding to dopamine D1 receptors was studied using [3H]SCH 23390. Antagonist binding of dopamine D2 receptors was performed with [3H]spiperone. At both ages no differences were found between SHR and WKY in affinity (Kd) or concentration (Bmax) of dopamine D1 and D2 receptors. Binding to the high affinity state of the dopamine D2 receptor was measured using the agonist [3H]N-n-propylnorapomorphine (NPA). No differences in Bmax or Kd were found between SHR and WKY at both ages studied, indicating that the ratio between dopamine D2 receptors in the high and in the low affinity state is not altered in spontaneous hypertension. Although the results do not reveal differences in affinities or concentrations of dopamine D1 or D2 receptors in the caudate nucleus between SHR and WKY, a role in the development of hypertension for the here described lack of receptor up-regulation in connection with our previous observation of lower release of dopamine in the caudate nucleus of SHR, cannot be excluded.
Linthorst
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AC
Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
De Jong
W
W
De Boer
T
T
Versteeg
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DH
D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012016:Reference Values
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine