CHARACTERIZATION OF ALPHA-1 ADRENERGIC-RECEPTORS LINKED TO [H-3] INOSITOL METABOLISM IN RAT CEREBRAL-CORTEX

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (2) , 317-323
Abstract
The properties of .alpha.-1 adrenergic receptors in rat cerebral cortex were examined by measuring increases in [3H]inositol tritium labeled metabolism in brain slices. Rat cerebral cortex slices were incubated in the presence of 0.23 .mu.M [3H]inositol in Krebs-Ringer-bicarbonate buffer containing 10 mM LiCl2, and the production of H2O soluble [3H]inositol phosphates was monitored after extraction and anion-exchange chromatography. Norepinephrine caused a 4- to 6-fold increase in [3H]inositol metabolism in cerebral cortical slices. This response was blocked much more potently by the .alpha.-1-selective antagonist prazosin than by the .alpha.-2-selective antagonist yohimbine. Epinephrine and norepinephrine were full agonists and stimulated [3H]inositol metabolism to the same extent in this system. The synthetic drugs phenylephrine and methoxamine were partial agonists at these receptors, with intrinsic activities only 56-58% of epinephrine and norepinephrine. Various imidazoline and other partial agonists caused no measurable stimulation of [3H]inositol metabolism in this preparation. The response to norepinephrine was completely blocked by .alpha. adrenergic receptor antagonists with the potency order prazosin > BE 2254 [3,4-dihydro-2-[[[2-(4-hydroxyphenyl)ethyl]amino]methyl]-1(2H)-naphthalenone] > indoramin = phentolamine > azapetine > piperoxan > yohimbine. In the absence of Ca, basal [3H]inositol metabolism was increased, but norepinephrine caused the same 5-fold stimulation as in the presence of 2.5 mM CaCl2. The potencies of both antagonists and agonists in inhibiting or activating [3H]inositol metabolism in rat cerebral cortex slices were highly correlated with their ability to displace the .alpha.-1 adrenergic receptor selective radioligand [125I]BE 2254 from specific binding sites in membrane preparations of rat cerebral cortex. This response should be a useful measure of .alpha.-1 adrenergic receptor responsiveness in brain tissue.