Effect of aging on alpha-1 adrenergic stimulation of phosphoinositide hydrolysis in various regions of rat brain.
The effects of aging were examined on the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis in three brain regions. Tissue minces of thalamus, cerebral cortex and hippocampus from 3-, 18- and 28-month-old male Fischer 344 rats were prelabeled with [3H]myoinositol. Exposure of these prelabeled minces to phenylephrine and (-)-norepinephrine revealed that accumulation of [3H]inositol phosphates was selectively reduced by 20 to 30% in the thalamus and cerebral cortex of the oldest age group. Analysis of concentration-response and competition binding curves indicated that this decrease was due to diminished agonist efficacy rather than diminished receptor affinity. The reduction in responsiveness to phenylephrine and (-)-norepinephrine in the cerebral cortex and the lack of any changes in the hippocampus parallel previously reported changes in the density of alpha-1 adrenergic receptors with aging. These data indicate that the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis is reduced in some, but not all, brain regions of aged Fischer 344 rats.
Burnett
D M
DM
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
Bowyer
J F
JF
Masserano
J M
JM
Zahniser
N R
NR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*; D044024:Tetralones
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D007457:Iodine Radioisotopes; D010627:Phenethylamines; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; D010656:Phenylephrine; C010652:BE 2254; D009638:Norepinephrine