Norepinephrine and histamine potentiate the increases in cyclic adenosine 3':5'-monophosphate elicited by vasoactive intestinal polypeptide in mouse cerebral cortical slices: Mediation by α1-adrenergic and H1-histaminergic receptors

P. J. Magistretti, M. Schorderet

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Abstract

We have examined the interactions, in eliciting cAMP accumulation, between vasoactive intestinal polypeptide (VIP) and the three monoamines norepinephrine (NE), histamine (HIS), and serotonin (5-hydroxytryptamine, 5-HT) in mouse cerebral cortical slices. We have observed that NE and HIS, but not 5-Ht, act synergistically with VIP to increase cAMP levels. The rank-order of potency of several adrenergic agonists in potentiating the effect of VIP on cAMP levels is the following: epinephrine > NE > phenylephrine >> clonidine, with EC50 of 2.2, 5, and 10 μM, respectively (clonidine being only marginally effective). This pharmacological profile is characteristic of the activation of α1-adrenergic receptors. This contention is substantiated by the observation that the potentiating effect of NE is antagonized by the selective α1-adrenergic antagonist prazosin at nanomolar concentrations. The potentiating effect of HIS is mediated by H1-histaminergic receptors since it is antagonized by the selective H1-receptor antagonist mepyramine but not by cimetidine, a selective H2-receptor antagonist. The synergistic interaction between VIP and NE is also observed in the presence of the adenosine antagonist theophylline, thus discarding the possibility of a mediation of the synergism by adenosine released by VIP. In view of the morphological and physiological properties of the VIP intracortical neuronal system and the noradrenergic projection to the cerebral cortex, it appears that sensory stimulation may constitute a behavioral event whereby the synergism between VIP and NE may become operative and lead to a drastic increase in the levels of cAMP within a discrete cortical volume delineated by the intersection of the tangentially organized noradrenergic fibers and a group of activated, radially oriented VIP intracortical neurons.

Original languageEnglish (US)
Pages (from-to)362-368
Number of pages7
JournalJournal of Neuroscience
Volume5
Issue number2
DOIs
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Neuroscience(all)

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