Modulation of histamine release and synthesis in the brain mediated by alpha 2-adrenoceptors.
The adrenergic regulation of histamine release was studied in rat brain slices labeled with L-[3H]histidine. Noradrenaline in increasing concentrations progressively inhibited K+-evoked [3H]histamine release from cortical slices, whereas phenylephrine and isoprenaline were ineffective. Yohimbine, a preferential alpha 2-adrenoceptor antagonist, reversed the noradrenaline effect in an apparently competitive manner and with a mean Ki value of 30 nM. Phentolamine reversed the noradrenaline effect with a similar potency, whereas propranolol was ineffective. The imidazolines clonidine and oxymetazoline acted as partial agonists, oxymetazoline even behaving as an apparent antagonist. In vivo clonidine also inhibited [3H]histamine formation in cerebral cortex, an effect reversed by the administration of yohimbine. However, yohimbine failed to increase significantly [3H]histamine release in vitro and [3H]histamine formation in vivo, suggesting that adrenergic receptors are not activated by endogenous noradrenaline released under basal conditions. It is concluded that adrenergic alpha 2-adrenoceptors presumably located on histaminergic axons control release and synthesis of histamine in the brain.
Gulat-Marnay
C
C
Laboratoire de Physiologie, Faculté de Pharmacie, Centre Paul Broca, Paris, France.
Lafitte
A
A
Arrang
J M
JM
Schwartz
J C
JC
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D006632:Histamine / Q000096:biosynthesis / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D006633:Histamine Antagonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D006632:Histamine; D003000:Clonidine; D011188:Potassium; D009638:Norepinephrine