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N C Schaad

Publications and source records attributed to N C Schaad.

25 records · Page 2Linked to original sources
PubMed1992

Rat pineal Gsa, Gia and Goa: relative abundance and development.

The adult rat pineal gland contains relatively high concentrations of Gsa, low amounts of both Gia and Goa, and undetectable levels of GTa. During development the amounts of 45 kDa Gsa and of Gia remain constant. In contrast, 42 kDa Gsa and Goa are nearly absent at birth and increase in abundance markedly thereafter. GTa is undetectable at any age. It would appear that multiple mechanisms regulate the expression of G-proteins in the pineal gland.

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PubMed1992

Characterization of alpha 2-adrenergic receptors on rat pinealocytes.

alpha 2-Adrenergic receptors in rat pineal membranes were characterized using p-[125I]iodoclonidine, a highly selective, high specific activity ligand. Binding was rapid (association constant rate = 0.0462 nM/min-1) and reversible after the addition of phentolamine (apparent dissociation rate constant = 0.04 min-1). Saturation experiments indicate the presence of a single class of noncooperative binding sites, with an equilibrium binding constant (Kd) of 1.1 +/- 0.3 nM and a binding capacity (Bmax) of 69 +/- 9 fmol/mg protein. Analysis of the relative potency of selected adrenoreceptor agonists and antagonists in competition studies with p-[125I]iodoclonidine indicates that the ligand is binding to a member of the family of alpha 2-adrenergic receptors that has a high affinity for oxymetazoline, phentolamine, and (-)norepinephrine and a low affinity for prazosin, similar to the recently described alpha 2-adrenergic receptor present in the bovine pineal gland, classified as belonging to the newly described alpha 2D-adrenergic receptor subtype. Rat pineal alpha 2-adrenergic receptors were unaltered after nerve endings degenerated. This observation and the recent finding that alpha 2-adrenergic agonists potentiate N6,2'-O-dibutyryl-cAMP or isobutylmethylxanthine stimulation of arylalkylamine N-acetyltransferase in the rat pineal gland establish that alpha 2D-like adrenergic receptors are located on pinealocytes.

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PubMed1991

Photoneural control of the synthesis and phosphorylation of pineal MEKA (phosducin).

MEKA is an acidic 33-kilodalton phosphoprotein found in the retina and pineal gland. It is of interest because it forms a cytoplasmic heterotrimer with the beta gamma-complex of GTP-binding regulatory proteins (G proteins). Accordingly, MEKA may play a role in signal transduction. MEKA is phosphorylated on Ser73 by cAMP-dependent protein kinase. In the present report, MEKA was studied using an antiserum (Anti-32) against MEKA65-96, which can be used to estimate total MEKA and the phosphorylation state of MEKA. It was confirmed that MEKA is rapidly phosphorylated by adrenergic stimulation of pineal glands in organ culture. In addition, total (dephosphorylated) MEKA was observed to increase after a 6-h treatment with norepinephrine or (Bu)2 cAMP, an effect which was dependent upon new protein synthesis. In in vivo studies, it was found that the total amount of MEKA and MEKA phosphorylation were increased at night in the dark, a time when the pineal gland is adrenergically stimulated. The high level of phosphorylation was rapidly reduced when animals were exposed to light, which blocks neural stimulation of the gland. This report provides the first in vivo evidence that MEKA phosphorylation is under physiological control, and that MEKA synthesis is controlled by an adrenergic----cAMP mechanism which requires protein synthesis.

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PubMed1989

Accumulation of cyclic AMP elicited by vasoactive intestinal peptide is potentiated by noradrenaline, histamine, adenosine, baclofen, phorbol esters, and ouabain in mouse cerebral cortical slices: studies on the role of arachidonic acid metabolites and protein kinase C.

In mouse cerebral cortical slices, noradrenaline (NA) potentiates cyclic AMP (cAMP) accumulation elicited by vasoactive intestinal peptide (VIP) through alpha 1-adrenergic receptors. This synergism is inhibited by indomethacin, and the prostaglandins E2 and F2 alpha mimic the effect of NA. In the present study, we observed that the synergism between VIP and NA is not inhibited by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) or the diacylglycerol-lipase inhibitor RHC 80267, thus further stressing the role of phospholipase A2 activation. Various neuroactive agents that potentiate the stimulatory effect of VIP on cAMP formation were also examined. As with NA, the potentiation by histamine and adenosine is inhibited by indomethacin. In contrast to NA, histamine, and adenosine, the synergistic interaction between phorbol esters and VIP on cAMP formation is abolished by H-7 but not by indomethacin. The potentiation by baclofen, a gamma-aminobutyric acidB receptor agonist, is partially inhibited by the 5-lipoxygenase inhibitor nafazatrom. The synergism between ouabain and VIP is reduced by H-7 but not by indomethacin and nafazatrom. These data indicate that the stimulation of cAMP formation elicited by VIP is under the modulation of various neuroactive agents that trigger diverse intracellular mechanisms to potentiate the effect of the peptide.

Adenosine↗
PubMedDate not supplied

Effects of ethanol on VIP-and/or noradrenaline-stimulated cAMP formation in mouse brain.

Among several effects, ethanol (EtOH) interferes with membrane fluidity and lipid-protein interactions. As proteins are influenced by surrounding lipids, the activity of membrane-bound enzymes such as adenylate cyclase (AC) could be modulated by EtOH, as shown in potentiating, at toxic concentrations, the stimulating effect of hormones or neurotransmitters. We have also found that EtOH potentiates in a dose-dependent manner (EC50 = 100 mM) the cAMP production elicited by vasoactive intestinal peptide (VIP), already noticeably at 70 mM, without affecting basal cAMP levels (up to 400 mM). Propanol produces a similar potentiation, whereas methanol was inactive. Butanol (200 mM) displays toxic effects. The potentiation induced by EtOH is similar for peptide- (VIP) or monoamine- (noradrenaline) stimulated cAMP formation, suggesting a primary action at a interaction between VIP and NA in stimulating cAMP formation.

Animals↗
PubMedDate not supplied

Prostaglandins and the synergism between VIP and noradrenaline in the cerebral cortex.

We have previously shown that vasoactive intestinal peptide (VIP) and noradrenaline (NA) interact synergistically to increase cyclic AMP levels in mouse cerebral cortical slices. The pharmacological mechanism of this synergism is the potentiation by NA, through alpha 1 adrenergic receptors, of the stimulatory effect of VIP on cAMP formation. A similar interaction has been confirmed in guinea pig cerebral cortex and in discrete nuclei of the rat hypothalamus. Furthermore VIP and NA interact synergistically to depress the spontaneous activity of identified neurons in rat neocortex. At the cellular level, this synergistic interaction suggests that VIP- and NA-containing neuronal systems may converge, at least in part, on the same target cells to increase cAMP levels in the cerebral cortex. At the molecular level, the interaction may occur at various steps in signal transduction, between receptors, intramembrane transduction processes or intracellular effector mechanisms. Here we report that the alpha 1-adrenergic potentiation of the increases in cAMP elicited by VIP involves the formation of arachidonic acid metabolites and is mimicked by prostglandins F2 alpha and E2.

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