Comparison of postnatal changes in alpha 1-adrenoceptor binding and adrenergic stimulation of phosphoinositide hydrolysis in rat cerebral cortex.
Adrenergic stimulation of phosphoinositide hydrolysis is mediated by the alpha 1-adrenoceptor subtype in many tissues including the brain. We have investigated the coupling of alpha 1-adrenoceptors to phosphoinositide hydrolysis during ontogeny. Alpha 1-adrenoceptor number and affinity were measured using [3H]prazosin binding in crude membranes of cerebral cortex and compared to the ability of the adrenergic agonists norepinephrine (NE) and phenylephrine (PE) to stimulate the formation of [3H] inositol phosphates from [3H]myo-inositol in brain slices at various ages. The greatest changes in the developmental expression of both the Bmax for [3H]prazosin binding and maximal (10(-4)M) NE- or PE-stimulated [3H]inositol phosphates were observed during the period of 7-21 days of age. No changes in the KD for [3H]prazosin were observed. However, at 14 days of age the EC50 for NE but not PE stimulation of [3H]inositol phosphates was slightly but significantly lower than at later ages. To quantitatively compare these two parameters during ontogeny, data were expressed as a percentage of the adult (greater than 65 day) value. At early ages (7 and 14 days) but not at later ages (21 and 37 days) the percent expression of [3H]prazosin binding sites was significantly greater than the maximal NE-stimulated [3H]inositol phosphates. This suggests that early in neonatal development alpha 1 adrenoceptors in brain are not tightly coupled to phosphoinositide hydrolysis.
Schoepp
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Rutledge
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D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D006150:Guanine Nucleotides / Q000494:pharmacology; D006868:Hydrolysis; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000378:metabolism*; D013566:Sympathomimetics / Q000494:pharmacology*
D006150:Guanine Nucleotides; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D013566:Sympathomimetics; D010656:Phenylephrine; D009638:Norepinephrine; D011224:Prazosin