Evidence that two stereochemically different alpha-2 adrenoceptors modulate norepinephrine release in rat cerebral cortex

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Cerebral cortex slices from the rat were loaded with [3H]norepinephrine ([3H]NE) and superfused in order to measure the release of radioactivity at rest and in response to electrical stimulation. The (-)-isomer and the (+)-isomer of CH-38083 {[7,8-(methylenedioxy)-14-α-hydroxyalloberbane HCl}, a selective alpha-2 adrenoceptor antagonist with an alloberbane skeleton, increased the electrically induced release of [3H]NE in a concentration dependent manner, and a similar effect was observed with racemic CH-38083 and idazoxan. The stereoisomers of CH-38083 applied in a concentration range of 10-8 to 10-6 mol/l were equipotent in facilitating stimulation-evoked [3H]NE release: concentrations needed to enhance tritium outflow by 50% were 1.3 x 10-7 mol/l for (-)-CH-38083 and 1.4 x 10-7 mol/l for (+)-CH-38083. Exogenous NE decreased the electrically stimulated release of [3H]NE, and the stereoisomers of CH-38083 antagonized this inhibition with different potencies: the dissociation constant (K(B)) values for (-)-isomer and for (+)-isomer of CH-38083 were 14.29 and 97.18 nmol/l. These data indicate that presynaptic alpha-2 adrenoceptors that are available for NE released from axon terminals do not show stereospecificity toward enantiomers of CH-38083, whereas those that are occupied by exogenous NE are much more sensitive toward (-)CH-38083. The alpha-1 adrenoceptor antagonist prazosin also differentiated between the alpha-2 adrenoceptor subtypes: prazosin (10-6 mol/l) did not alter the increase of electrically induced [3H]NE release evoked by (-)- and (+)-CH-38083; however, in its presence, the stereoisomers of CH-38083 failed to antagonize the inhibitory effect of exogenous NE on its own release. It is concluded that presynaptic alpha-2 adrenoceptors involved in modulation of NE release from rat cerebral cortex do not represent a homogeneous population of receptors, but rather are composed of at least two subtypes with different functions in the neurotransmitter release process.

Original languageEnglish
Pages (from-to)44-49
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
Publication statusPublished - Jan 1 1991

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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