Decreased alpha 1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain.
The expression of alpha 1-adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125I-2-[beta-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125I-HEAT bound selectively to alpha 1-adrenergic receptors. Specific binding of 125I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of alpha 1-adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the alpha 1-adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of alpha 1-adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D006868:Hydrolysis; D006973:Hypertension / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D007457:Iodine Radioisotopes; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010627:Phenethylamines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013403:Sugar Phosphates / Q000378:metabolism*; D044024:Tetralones
D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D007457:Iodine Radioisotopes; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D013403:Sugar Phosphates; D044024:Tetralones; C010652:BE 2254; D002217:Carbachol; D009638:Norepinephrine