TY - JOUR
T1 - Norepinephrine and histamine potentiate the increases in cyclic adenosine 3':5'-monophosphate elicited by vasoactive intestinal polypeptide in mouse cerebral cortical slices
T2 - Mediation by α1-adrenergic and H1-histaminergic receptors
AU - Magistretti, P. J.
AU - Schorderet, M.
PY - 1985
Y1 - 1985
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0021922462&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.05-02-00362.1985
DO - 10.1523/jneurosci.05-02-00362.1985
M3 - Article
C2 - 2983040
AN - SCOPUS:0021922462
SN - 0270-6474
VL - 5
SP - 362
EP - 368
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 2
ER -