Response to cardiac sympathetic activation in transgenic mice overexpressing beta 2-adrenergic receptor

1996 ◽  
Vol 271 (2) ◽  
pp. H630-H636 ◽  
Author(s):  
X. J. Du ◽  
E. Vincan ◽  
D. M. Woodcock ◽  
C. A. Milano ◽  
A. M. Dart ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Nerve Stimulation ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Adrenergic Stimulation ◽  
Adrenergic Activity ◽  
Beta 2 ◽  
Stimulation Of

Transgenic mice have been created with 200-fold overexpression of beta 2-adrenergic receptors specifically in the heart. Cardiac function was studied in these transgenic mice and their controls at baseline and during isoproterenol perfusion or sympathetic nerve stimulation. The model used was an in situ buffer-perfused, innervated heart, and the left ventricle maximal derivative of pressure over time (dP/dtmax) and heart rate (HR) were measured. Basal HR and dP/dtmax were 30-40% higher in hearts from transgenic mice than controls. Electrical stimulation of sympathetic nerves (2, 4, and 8 Hz) or infusion of isoproterenol markedly increased HR and dP/dtmax in control hearts. Hearts from transgenic mice did not respond to isoproterenol. However, hearts from transgenic mice retained the HR response to nerve stimulation, and a small increase in dP/dtmax was also detected. Atenolol inhibited the response to nerve stimulation in control hearts but not that in hearts from transgenic mice. ICI-118551 inhibited the response in transgenic hearts. Basal HR and dP/dtmax were decreased by ICI-118551 only in transgenic hearts. Thus overexpression of cardiac beta 2-receptors modifies beta-adrenergic activity, but the responses to endogenous and exogenous adrenergic stimulation are affected differently.

Heightened α1A-adrenergic receptor activity suppresses ischaemia/reperfusion-induced Ins(1,4,5)P3 generation in the mouse heart: a comparison with ischaemic preconditioning

2007 ◽  
Vol 114 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Fatemeh Amirahmadi ◽  
Lynne Turnbull ◽  
Xiao-Jun Du ◽  
Robert M. Graham ◽  
Elizabeth A. Woodcock
Keyword(s):  
Transgenic Mice ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Mouse Heart ◽  
Ischaemic Preconditioning ◽  
Receptor Signalling ◽  
Ischaemia Reperfusion ◽  
Ischaemia And Reperfusion ◽  
Ischaemic Insult ◽  
Stimulation Of

Reperfusion of ischaemic rat or mouse hearts causes NE [noradrenaline (‘norepinephrine’)] release, stimulation of α1-ARs (α1-adrenergic receptors), PLC (phospholipase C) activation, Ins(1,4,5)P3 generation and the development of arrhythmias. In the present study, we examined the effect of increased α1A-AR drive on these responses. In hearts from non-transgenic mice (α1A-WT), Ins(1,4,5)P3 generation was observed after 2 min of reperfusion following 30 min of zero-flow ischaemia. No Ins(1,4,5)P3 response was observed in hearts from transgenic mice with 66-fold overexpression of α1A-AR (α1A-TG). This was despite the fact that α1A-TG hearts had 8–10-fold higher PLC responses to NE than α1A-WT under normoxic conditions. The immediate phospholipid precursor of Ins(1,4,5)P3, PtdIns(4,5)P2, responded to ischaemia and reperfusion similarly in α1A-WT and α1A-TG mice. Thus the lack of Ins(1,4,5)P3 generation in α1A-TG mice is not caused by limited availability of PtdIns(4,5)P2. Overall, α1-AR-mediated PLC activity was markedly enhanced in α1A-WT mice under reperfusion conditions, but responses in α1A-TG mice were not significantly different in normoxia and post-ischaemic reperfusion. Ischaemic preconditioning prevented Ins(1,4,5)P3 generation after 30 min of ischaemic insult in α1A-WT mice. However, the precursor lipid PtdIns(4,5)P2 was also reduced by preconditioning, whereas heightened α1A-AR activity did not influence PtdIns(4,5)P2 responses in reperfusion. Thus preconditioning and α1A-AR overexpression have different effects on early signalling responses, even though both prevented Ins(1,4,5)P3 generation. These studies demonstrate a selective inhibitory action of heightened α1A-AR activity on immediate post-receptor signalling responses in early post-ischaemic reperfusion.

Activation of Hageman Factor by α-Adrenergic Stimulation

1970 ◽  
Vol 23 (03) ◽  
pp. 417-422 ◽  
Author(s):  
D. G McKay ◽  
J.-G Latour ◽  
Mary H. Parrish
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Adrenergic Receptor ◽  
Adrenergic Stimulation ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Receptor Sites ◽  
High Doses ◽  
Stimulation Of

SummaryThe infusion of epinephrine in high doses produces disseminated intravascular coagulation by activation of Hageman factor. The effect is blocked by phenoxybenz-amine and is therefore due to stimulation of α-adrenergic receptor sites.

scholarly journals Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors.

1993 ◽  
Vol 268 (5) ◽  
pp. 3201-3208
Author(s):  
S. Pippig ◽  
S. Andexinger ◽  
K. Daniel ◽  
M. Puzicha ◽  
M.G. Caron ◽  
...  
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Kinase ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Beta 2

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

α-Adrenergic receptor modulation of the intrathoracic efferent sympathetic nervous system regulating the canine heart

1989 ◽  
Vol 67 (10) ◽  
pp. 1199-1204 ◽  
Author(s):  
J. A. Armour
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Blocking Agent ◽  
Sympathetic Ganglia ◽  
Canine Heart ◽  
Receptor Modulation ◽  
Adrenergic Antagonist ◽  
Cervical Ganglia ◽  
Β Adrenergic Receptors ◽  
Stimulation Of

The augmentation of ventricular inotropism induced by electrical stimulation of acutely decentralized efferent sympathetic preganglionic axons was reduced, but still present, following administraiton of hexamethonium (10 mg/kg i.v.). While hexamethonium continued to be administered, the cardiac augmentations so induced were enhanced significantly following administration of the α-adrenergic receptor blocking agent, phentolamine myselate (1 mg/kg i.v.). Stimulation of the sympathetic efferent postganglionic axons in cardiopulmonary nerves induced cardiac augmentations that were unchanged following administration of these agents singly or together. The cardiac augmentations induced by stimulation of efferent preganglionic sympathetic axons were unchanged when phentolamine was administered alone. The augmentations of cardiac inotropism induced by efferent postganglionic sympathetic axonal stimulation were decreased following local administration of the β-adrenergic antagonist timolol into the ipsilateral stellate and middle cervical ganglia. Thereafter, these augmentations were unchanged following the subsequent intravenous administration of phentolamine. It is concluded that the activation of cardiac neurons in the stellate and middle cervical ganglia by stimulation of efferent preganglionic sympathetic axons can be modified by α-adrenergic receptors and that these effects are dependent upon β-adrenergic receptors, not nicotinic ones, in intrathoracic ganglia.Key words: α-adrenergic inotropism, sympathetic ganglia, hexamethonium, phentolamine.

Adrenergic stimulation of inositol phosphate accumulation in tracheal epithelium

1989 ◽  
Vol 66 (1) ◽  
pp. 504-508 ◽  
Author(s):  
T. Bainbridge ◽  
R. D. Feldman ◽  
M. J. Welsh
Keyword(s):  
Adrenergic Receptor ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Second Messengers ◽  
Receptor Activation ◽  
Adrenergic Stimulation ◽  
Cl Secretion ◽  
Phosphate Accumulation ◽  
Inositol Phosphate Accumulation ◽  
Stimulation Of

To determine whether inositol phosphates are important second messengers in the regulation of Cl- secretion by airway epithelia, we examined the relationship between inositol phosphate accumulation and Cl- secretion in response to adrenergic agonists. We found that epinephrine stimulated Cl- secretion and inositol phosphate accumulation with similar concentration dependence. Although isoproterenol stimulated Cl- secretion, there was no effect of beta-adrenergic receptor activation on inositol phosphate accumulation. In contrast, alpha 1-adrenergic receptor activation stimulated inositol phosphate accumulation but failed to induce Cl- secretion. Another Cl- secretagogue, prostaglandin E1, also failed to stimulate inositol phosphate accumulation. These data suggest that inositol phosphate accumulation is neither sufficient nor required for stimulation of Cl- secretion in cultured canine tracheal epithelial cells.

Modulation of beta-adrenergic receptor-stimulated lipolysis in the heart by prostaglandins

1996 ◽  
Vol 271 (3) ◽  
pp. E556-E562
Author(s):  
Y. Ruan ◽  
H. Kan ◽  
C. Cano ◽  
K. U. Malik
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Rabbit Heart ◽  
Receptor Activation ◽  
Prostaglandin Synthesis ◽  
Prostaglandin I2 ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Endogenous Prostaglandin ◽  
Stimulation Of

The purpose of the present study was to investigate the contribution of prostaglandins to lipolysis elicited by beta-adrenergic receptor activation in the heart. We have studied the effect of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), and their precursor arachidonic acid (AA) in the presence and absence of a cyclooxygenase inhibitor, sodium meclofenamate, on glycerol output elicited by stimulation of beta-adrenergic receptors in the isolated rabbit heart with isoproterenol (ISOP). Bolus injections of ISOP (475 pmol) produced a constant increase in glycerol and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output. Infusion of sodium meclofenamate (16 microM) reduced basal and attenuated ISOP-induced 6-keto-PGF1 alpha output and enhanced glycerol output. During inhibition of endogenous prostaglandin synthesis with meclofenamate, infusion of PGI2 or PGE2 (0.1-1 microM) inhibited ISOP-induced glycerol output. Infusion of AA (0.1-1 microM) increased 6-keto-PGF1 alpha and reduced glycerol output. Infusion of sodium meclofenamate abolished the effect of AA to increase 6-keto-PGF1 alpha and to decrease glycerol output. These data suggest that prostaglandins synthesized in the heart act as an inhibitory modulator of beta-adrenergic receptor-stimulated cardiac lipolysis.

T3 potentiates the adrenergic stimulation of type II 5'-deiodinase activity in cultured rat brown adipocytes

1996 ◽  
Vol 271 (1) ◽  
pp. E15-E23 ◽  
Author(s):  
A. Hernandez ◽  
M. J. Obregon
Keyword(s):  
Protein Synthesis ◽  
Adrenergic Receptors ◽  
Inhibitory Action ◽  
De Novo ◽  
Type Ii ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic Receptors ◽  
Brown Adipocytes ◽  
De Novo Protein Synthesis ◽  
Stimulation Of

Iodothyronine type II 5'-deiodinase (5'D-II) activities were studied in cultures of rat brown adipocytes. In the presence of serum, the adrenergically stimulated 5'D-II activities were very low. In the absence of serum, adenosine 3',5'-cyclic monophosphate (cAMP) analogues stimulated 5'D-II activity. Thyroxine (T4) inhibited these increases. Norepinephrine slightly increased 5'D-II activity in hypothyroid conditions, but 3,5,3'-triiodothyronine (T3) strongly potentiated the adrenergic stimulation of 5'D-II (20-fold). T3 amplification of the adrenergic stimulation was via beta-adrenergic receptors, specifically mimicked by beta3-agonists, but it was not observed using cAMP analogues. The stimulatory effect of T3 predominated over the inhibitory action of T4, increased with exposure to T3, and required de novo protein synthesis. The half-life of 5'D-II was 30 min, suggesting that stabilization of 5'D-II did not occur. The effect was only observed in differentiated adipocytes. Retinoic acid has similar although smaller effects than T3. In conclusion, the presence of T3 is required and strongly potentiates the noradrenergic stimulation of 5'D-II activity in rat brown adipocytes.

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