Modulating a modulator: biogenic amines at subthreshold levels potentiate peptide-mediated cardioexcitation of the heart of the tobacco hawkmoth Manduca sexta.

1994 ◽  
Vol 197 (1) ◽  
pp. 377-391 ◽  
Author(s):  
K R Prier ◽  
O H Beckman ◽  
N J Tublitz
Keyword(s):  
Cyclic Amp ◽  
Manduca Sexta ◽  
Biogenic Amine ◽  
Molecular Mechanisms ◽  
Adult Heart ◽  
The Central Nervous System ◽  
Messenger System ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Dependent Mechanism

The central nervous system of the moth Manduca sexta contains a group of myoregulatory neuropeptides, the CAPs (Cardioacceleratory Peptides), which cause a physiologically important, dose-dependent increase in heart rate during wing inflation and flight in adult moths. We report here that the response of the adult heart to a subset of the CAPs, the CAP2S, is potentiated nearly twofold in the chronic presence of subthreshold levels of the biogenic amine octopamine or near-threshold levels of the biogenic amine serotonin. Subthreshold levels of the CAP2S fail to alter the response of the heart to octopamine. We have begun to investigate the molecular mechanisms underlying this potentiation. Previous work on the adult heart has shown that the CAP2s act through an inositol-1,4,5-trisphosphate second-messenger system. Here, we demonstrate that the cardioexcitatory effects of the two amines, in contrast to those of the CAP2S, are both mediated by cyclic AMP. Application to the heart of either 10(-5) moll-1 octopamine or 10(-6)moll-1 serotonin elicits a threefold increase in intracellular cyclic AMP levels. The CAP2S have no effect on cyclic AMP levels in the heart. These results illustrate a mechanism by which the effectiveness of a neurohormone can be increased with minimal cost to the animal. In Manduca sexta, subthreshold levels of octopamine are found in the haemolymph during wing inflation and flight. Thus, it is possible that octopamine up-regulates the effects of CAP2 via a cyclic-AMP-dependent mechanism during these activities.

Mechanisms of ACTH- and angiotensin II-stimulated 1α-hydroxycorticosterone secretion in the dogfish, Scyliorhinus canicula

1993 ◽  
Vol 10 (3) ◽  
pp. 235-244 ◽  
Author(s):  
K J Armour ◽  
L B O'Toole ◽  
N Hazon
Keyword(s):  
Angiotensin Ii ◽  
Cyclic Amp ◽  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Extracellular Calcium ◽  
Scyliorhinus Canicula ◽  
Interrenal Gland ◽  
Messenger System ◽  
Dose Dependent Increase ◽  
Dose Dependent

ABSTRACT An isolated perifused interrenal gland preparation from the lesser-spotted dogfish, Scyliorhinus canicula, was used to investigate the mechanisms of action of ACTH and angiotensin II (AII) on elasmobranch adrenocortical cells. ACTH-stimulated 1α-hydroxycorticosterone secretion was unaffected by dantrolene and significantly decreased in the absence of extracellular calcium. Dibutyryl cyclic AMP produced a dose-dependent increase in 1α-hydroxycorticosterone secretion. The results suggest that the mechanism of ACTH action in elasmobranchs may be similar to that reported for mammals and amphibians, involving the synergistic action of calcium with the cyclic AMP messenger system. AII-stimulated 1α-hydroxycorticosterone secretion was significantly inhibited in the presence of dantrolene and in the absence of extracellular calcium, indicating that both extracellular and intracellular calcium are required for the full action of AII. These results are consistent with results in mammals and amphibians where AII stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and changes in intracellular calcium concentration, and they suggest that AII may operate via this mechanism to stimulate 1α-hydroxycorticosterone secretion in elasmobranchs.

Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide

1990 ◽  
Vol 259 (6) ◽  
pp. G934-G939 ◽  
Author(s):  
M. W. Mulholland ◽  
S. Jaffer
Keyword(s):  
Myenteric Plexus ◽  
Acetylcholine Release ◽  
Calcitonin Gene Related Peptide ◽  
Ach Release ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Dependent Mechanism ◽  
Stimulation Of

The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.

Ionotropic glutamate receptor activation increases intracellular calcium in prolactin-releasing cells of the adenohypophysis

2006 ◽  
Vol 291 (6) ◽  
pp. E1188-E1196 ◽  
Author(s):  
Frederick P. Bellinger ◽  
Bradley K. Fox ◽  
Wing Yan Chan ◽  
Lori K. Davis ◽  
Marilou A. Andres ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Anterior Pituitary ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Pituitary Cells ◽  
The Central Nervous System ◽  
To Receive ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
The Brain

Endocrine cells of the anterior pituitary are controlled by the central nervous system through hormonal interactions and are not believed to receive direct synaptic connections from the brain. Studies suggest that some pituitary cells may be modulated by the neurotransmitter glutamate ( 5 , 16 ). We investigated prolactin (PRL)-releasing cells of the anterior pituitary of a euryhaline fish, the tilapia ( Oreochromis mossambicus), for the presence of possible glutamate receptors (GluRs). Fura-2 imaging addressed the ability of glutamate to increase intracellular calcium. We observed a dose-dependent increase in intracellular calcium with transient perfusion (1–2 min) of glutamate (10 nM to 1 mM) in two-thirds of imaged cells. This increase was attenuated by the ionotropic GluR antagonist kynurenic acid (0.5–1.0 mM). The increase was also blocked or attenuated by antagonists of L-type voltage-gated calcium channels. The GluR agonist α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA; 100 μM) produced intracellular calcium increases that were reversibly blocked by the selective AMPA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In contrast, the selective agonist N-methyl-d-aspartate (NMDA; 100 μM to 1 mM in magnesium-free solution with 10 μM glycine) had no effect on intracellular calcium. Radioimmunoassays demonstrated that glutamate stimulated PRL release. CNQX but not the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid blocked this release. Antibodies for mammalian AMPA- and NMDA-type GluR produced a similar punctate immunoreactivity in the periphery of PRL cells. However, the NMDA antibody recognized a protein of a different molecular mass in PRL cells compared with brain cells. These results clearly indicate the presence of GluRs on tilapia PRL cells that can stimulate PRL release.

scholarly journals Ecstasy intoxication: the toxicological basis for treatment

2003 ◽  
Vol 58 (6) ◽  
pp. 332-341 ◽  
Author(s):  
Maristela Ferigolo ◽  
Adriana G. da S. Machado ◽  
Niara B. Oliveira ◽  
Helena M. T. Barros
Keyword(s):  
Health Care Providers ◽  
Adverse Reactions ◽  
Oral Route ◽  
Acute Intoxication ◽  
Care Providers ◽  
Neurotoxic Effects ◽  
Ecstasy Intoxication ◽  
The Central Nervous System ◽  
Dose Dependent Increase ◽  
Dose Dependent

Youngsters are increasingly using 3,4 methylenedioxymethamphetamine, known as ecstasy, because it is wrongly believed that it does not induce harm. However, there are many reports of adverse effects, including acute intoxication, abuse potential, and possible neurotoxic effects. Therefore, health care providers need to promptly recognize the symptoms of systemic intoxication in order to initiate early treatment. The drug is used by the oral route for long hours during crowded dance parties. Acutely, ecstasy increases the release of serotonin and decreases its reuptake, leading to hypertension, hyperthermia, trismus, and vomiting. There is debate on whether recreational doses of ecstasy cause permanent damage to human serotonergic neurons. Ecstasy users showed a high risk of developing psychopathological disturbances. The prolonged use of ecstasy might induce dependence, characterized by tolerance and hangover. Acute ecstasy intoxication needs emergency-type treatment to avoid the dose-dependent increase in adverse reactions and in severity of complications. There are no specific antidotes to be used during acute intoxication. Supportive measures and medical treatment for each one of the complications should be implemented, keeping in mind that symptoms originate mainly from the central nervous system and the cardiovascular system.

scholarly journals Salmon calcitonin-induced stimulation of 1α,25-dihydroxycholecalciferol synthesis in rats involving a mechanism independent of adenosine 3′:5′-cyclic monophosphate

1979 ◽  
Vol 184 (2) ◽  
pp. 269-275 ◽  
Author(s):  
N Horiuchi ◽  
H Takahashi ◽  
T Matsumoto ◽  
N Takahashi ◽  
E Shimazawa ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Salmon Calcitonin ◽  
Rat Kidney ◽  
Plasma Concentrations ◽  
Maximal Effect ◽  
Balance Study ◽  
System A ◽  
Dose Dependent Increase ◽  
Dose Dependent

The effect of natural salmon calcitonin on accumulation in plasma of 1 alpha,25-dihydroxy-[3H]cholecalciferol from 25-hydroxy[3H]cholecalciferol in vivo was investigated in vitamin D-deficient thyroparathyroidectomized rats into which graded doses of the hormone were continuously infused by use of a balance study system. A dose-dependent increase in plasma concentrations of 1 alpha,25-dihydroxy[3H]cholecalciferol was observed with calcitonin infusion for 6–30h at a rate greater than 20 M.R.C. m-units/h. Infusion of parathyrin or cyclic AMP produced a similar stimulation [Horiuchi, Suda, Takahashi, Shimazawa & Ogata (1977) Endocrinoly 101, 969–974], but the maximal effect of calcitonin was additive to that of either parathyrin or cyclic AMP. Furthermore concurrent infusion of theophylline (0.5 mumol/h) did not potentiate the effect of submaximal doses (3 and 20 M.R.C. m-units/h) of calcitonin. Plasma concentrations of calcium showed a decrease with calcitonin infusion for 30h, but those of Pi remained unchanged. These results strongly suggest that the rat kidney is endowed with a calcitonin-sensitive 1 alpha-hydroxylase system that is separate from the parathyrin/cyclic AMP system and is independent of changes in plasma Pi.

PI3K is involved in PDGF-β receptor upregulation post-PDGF-BB treatment in mouse HSC

2006 ◽  
Vol 291 (6) ◽  
pp. G1051-G1061 ◽  
Author(s):  
Carmen G. Lechuga ◽  
Zamira H. Hernández-Nazara ◽  
Elizabeth Hernández ◽  
Marcia Bustamante ◽  
Gregory Desierto ◽  
...  
Keyword(s):  
Cell Activation ◽  
Molecular Mechanisms ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Quiescent Cells ◽  
Protein Pool ◽  
Receptor Upregulation ◽  
Β Receptor ◽  
Dose Dependent ◽  
Dependent Mechanism

Increased expression of PDGF-β receptors is a landmark of hepatic stellate cell activation and transdifferentiation into myofibroblasts. However, the molecular mechanisms that regulate the fate of the receptor are lacking. Recent studies suggested that N-acetylcysteine enhances the extracellular degradation of PDGF-β receptor by cathepsin B, thus suggesting that the absence of PDGF-β receptors in quiescent cells is due to an active process of elimination and not to a lack of expression. In this communication we investigated further molecular mechanisms involved in PDGF-β receptor elimination and reappearance after incubation with PDGF-BB. We showed that in culture-activated hepatic stellate cells there is no internal protein pool of receptor, that the protein is maximally phosphorylated by 5 min and completely degraded after 1 h by a lysosomal-dependent mechanism. Inhibition of receptor autophosphorylation by tyrphostin 1296 prevented its degradation, but several proteasomal inhibitors had no effect. We also showed that receptor reappearance is time and dose dependent, being more delayed in cells treated with 50 ng/ml (48 h) compared with 10 ng/ml (24 h).

scholarly journals Inhibition of A20 deubiquitinase activity by KSHV vFLIP: A SUMO dependent mechanism?

2019 ◽  
Author(s):  
Kevin Herold ◽  
Ayana Ruffin ◽  
Ashley Mitchell ◽  
Jennifer C. Chmura ◽  
Deirdre Johnson ◽  
...  
Keyword(s):  
Virus Production ◽  
Negative Regulator ◽  
Viral Reactivation ◽  
Small Molecule Inhibition ◽  
Lytic Reactivation ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Autophagy Inhibition ◽  
Insight Into ◽  
Dependent Mechanism

AbstractKSHV vFLIP is a potent activator of NFκB signaling and an inhibitor of apoptosis and autophagy. Inhibition of vFLIP function and NFκB signaling promotes viral reactivation. Here we provide evidence for a novel function of vFLIP in promoting NFκB signaling through inhibition of the DUB activity of the negative regulator, A20. We demonstrate interaction of vFLIP with the Itch/A20 ubiquitin editing complex. We have identified a SUMO interaction motif in vFLIP that is required for NFκB activation. We observed a decrease in vFLIP induced NFκB when the SIM in vFLIP was mutated. Small molecule inhibition of SUMOylation resulted in a dose dependent increase lytic reactivation and virus production. Our results suggest a role for SUMO in mediating vFLIP function and provide evidence for vFLIP modulation of the negative regulation of NFκB signaling by A20. Our results provide further insight into the function of vFLIP and SUMO in the regulation of NFκB signaling and the latent lytic transition.

scholarly journals Insect cardioactive peptides. II. Neurohormonal control of heart activity by two cardioacceleratory peptides in the tobacco hawkmoth, Manduca sexta

1985 ◽  
Vol 114 (1) ◽  
pp. 381-395 ◽  
Author(s):  
N. J. Tublitz ◽  
J. W. Truman
Keyword(s):  
Heart Rate ◽  
Manduca Sexta ◽  
Gel Filtration ◽  
Dependent Manner ◽  
Heart Activity ◽  
High Potassium ◽  
Calcium Dependent ◽  
Dose Dependent Increase ◽  
Dose Dependent

The physiological characteristics of two cardioacceleratory peptides (CAPs) were analysed in the tobacco hawkmoth, Manduca sexta, to determine if either CAP functioned as a cardioregulatory neurohormone. In vivo heart recordings from pharate and newly emerged adults revealed a dramatic increase in heart rate associated with wing-spreading behaviour. Bioassay of whole blood taken from wing-spreading (WS) animals indicated the presence of a stage-specific, blood-borne cardioacceleratory factor(s). Gel filtration of WS blood identified two cardioacceleratory factors which co-eluted with the two CAPs. A depletion of the ventral nerve cord levels of both CAPs was observed during WS behaviour. Measurements of blood CAP levels showed that the peak CAP titres were coincident with the initiation of WS behaviour. Experimental manipulations that delayed the onset of WS behaviour also prevented CAP release. High potassium incubation evoked the release of both CAPs in a calcium-dependent manner. In vivo injections of CAP1 or CAP2 caused a dose-dependent increase in heart rate. These results confirm the hypothesis that both CAPs function as cardioregulatory neurohormones during wing-spreading behaviour in Manduca sexta.

scholarly journals Insect cardioactive peptides. I. Distribution and molecular characteristics of two cardioacceleratory peptides in the tobacco hawkmoth, Manduca sexta

1985 ◽  
Vol 114 (1) ◽  
pp. 365-379 ◽  
Author(s):  
N. J. Tublitz ◽  
J. W. Truman
Keyword(s):  
Manduca Sexta ◽  
Isolated Heart ◽  
Gel Filtration ◽  
Biochemical Properties ◽  
Molecular Characteristics ◽  
Molecular Weights ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Pharate Adult

Using an in vitro heart bioassay, the pharmacological and biochemical properties of two cardioactive peptides derived from neural tissues of the moth, Manduca sexta, were analysed. Gel filtration of ventral nerve cords (VNC) from pharate adults identified two cardioacceleratory peptides (CAP1 and CAP2) with apparent molecular weights of 1000 and 500 Da, respectively. Both CAPs were localized to the abdominal perivisceral organs, the major neurohaemal release sites in the insect VNC. Pulse application of CAP1 or CAP2 on the in vitro Manduca heart produced a dose-dependent increase in rate but had no effect on beat amplitude. The threshold dose for the action of each peptide on the isolated heart bioassay was less than 0.05 abdominal nerve cord equivalents. Both CAPs were present in the pharate adult VNC of several other Lepidopteran species. Neither CAP1 nor CAP2 was detected in the prepupal VNC of Manduca sexta.

Centrally administered ouabain aggravates central sleep apneas

1993 ◽  
Vol 74 (2) ◽  
pp. 545-548 ◽  
Author(s):  
T. Sato ◽  
M. Tadokoro ◽  
H. Kaba ◽  
H. Saito ◽  
K. Seto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Eye Movement ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
The Central Nervous System ◽  
Freely Moving ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Lateral Cerebral Ventricle

The presence of endogenous digitalis-like factors in the central nervous system suggests their functional significance in the central nervous system. Three-day infusions of three-stepped doses of the digitalis agent ouabain (1–100 ng.kg body wt-1.h-1) into the lateral cerebral ventricle of freely moving rats caused a dose-dependent increase in the number of central-apneic episodes during rapid-eye-movement sleep without affecting the time spent in rapid-eye-movement sleep or basic respiratory rate. These results suggest that endogenous digitalis-like factors may be involved in the genesis of central sleep apneas.

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