Alpha 1-adrenergic receptors in neuronal cultures from rat brain: increased expression in the spontaneously hypertensive rat
| Autor: | Mohan K. Raizada, Colin Sumners, Anthony J. Pacitti, Judith B. Feldstein |
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| Rok vydání: | 1986 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Population Biochemistry Binding Competitive Rats Inbred WKY Cellular and Molecular Neuroscience Phenylephrine Phentolamine Spontaneously hypertensive rat Internal medicine Rats Inbred SHR Phenethylamines medicine Prazosin Animals education Receptor Cells Cultured Tetralones Neurons education.field_of_study business.industry Cell Membrane Brain Rats Inbred Strains Receptors Adrenergic alpha Yohimbine Rats Kinetics Endocrinology Hypertension business medicine.drug |
| Zdroj: | Journal of neurochemistry. 47(4) |
| ISSN: | 0022-3042 |
| Popis: | Neuronal cells in primary culture from 1-day-old brains of normotensive, Wistar-Kyoto strain (WKY) and spontaneously hypertensive (SH) rats have been utilized to study the expression of α1-adrenergic receptors. Binding of a selective α1 antagonist, [125I]2-[β-(4-hydroxy-3-iodophenyl)-ethylaminomethyl]-tetralone ([125I]HEAT) to neuronal membranes prepared from primary brain cultures of WKY and SH rats was 75–80% specific, rapid, and time-dependent although the binding was 1.5–2 times higher in neuronal membranes from SH rat brain cultures. Kinetic analysis of the association and dissociation data demonstrated no significant differences between rat strains. Competition-inhibition experiments provided IC50 values for various antagonists and agonists in the following order: prazosin < phentolamine < yohimbine < phenylephrine < norepinephrine < propranolol, suggesting that [125I]-HEAT bound selectively to α1-adrenergic receptors. Scatchard analysis of the binding data provided straight lines for both strains of rats, indicating the presence of a homogeneous population of binding sites. It also showed that the increase in the binding in neuronal cells from SH rat brains over those from normotensive WKY controls was a result of an increase in the number of α1-adrenergic receptors. Incubation of neuronal cultures from both strains of rats with phenylephrine, an α1-adrenergic agonist, caused a time- and dose-dependent decrease in the binding of [125I]HEAT. This decrease was due to a decrease in the number of α1-adrenergic receptors. In conclusion, we demonstrated that the expression of α1-adrenergic receptors in neuronal cultures of SH rat brain was increased compared with neuronal cultures from normotensive controls. We suggest that the elevated number of these receptors in neurons from the brains of SH rats is an intrinsic property of these cells and therefore provides an etiological basis for the predisposition of these animals to the hypertensive state. |
| Databáze: | OpenAIRE |
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