[3H]R-Terazosin binds selectively to α1-adrenoceptors over α2-adrenoceptors – comparison with racemic [3H]terazosin and [3H]prazosin

Ireland, Lynne M.; Cain, John Cannell; Rotert, Gary; Thomas, Samuel; Shoghi, Simin; Hancock, Arthur A.; Kerwin, James F.

doi:10.1016/s0014-2999(97)89681-1

Cited by 13 publications

(5 citation statements)

References 19 publications

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“…All the drugs and solutions were freshly prepared before the experiment and delivered using syringe pumps. The reported selectivity value (␣ 1 /␣ 2 adrenergic receptors) for corynanthine, prazosin, and cirazoline is 100, 1000 to 5000, and 50 to 100, respectively (Cavero et al, 1982;Doxey et al, 1984;Angel et al, 1995;Ireland et al, 1997).…”

Section: Retrograde Labeling Of Spinally Projecting Pvn Neuronsmentioning

confidence: 99%

Presynaptic α₁ Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Chen

Li²,

Pan³

2005

J Pharmacol Exp Ther

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The hypothalamic paraventricular nucleus (PVN) neurons that project to the spinal intermediolateral cell column and brainstem are important for the control of sympathetic outflow. Stimulation of ␣ 1 adrenergic receptors in the PVN increases sympathetic outflow, but the cellular mechanisms remain unclear. In this study, we determined the role of ␣ 1 adrenergic receptors in the regulation of glutamatergic and GABAergic synaptic inputs to spinally projecting PVN neurons. Whole-cell and cell-attached patch-clamp recordings were performed on retrogradely labeled PVN-spinal neurons in rat brain slices. Bath application of 10 to 100 M phenylephrine, an ␣ 1 adrenergic receptor agonist, significantly increased the frequency of spontaneous excitatory postsynaptic currents in a concentration-dependent manner. This effect was blocked by the ␣ 1 adrenergic receptor antagonists prazosin or corynanthine. Phenylephrine also significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) but not the amplitude and decay constant of mEPSCs. Furthermore, activation of ␣ 1 adrenergic receptors with phenylephrine or cirazoline significantly decreased the frequency of spontaneous inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents, and this effect also was blocked by corynanthine. In addition, 50 M phenylephrine significantly increased the firing rate of 13 labeled PVN neurons from 3.16 Ϯ 0.42 to 5.83 Ϯ 0.65 Hz. However, phenylephrine failed to increase the firing of most labeled PVN neurons in the presence of GABA A and ionotropic glutamate receptor antagonists. Thus, these data suggest that activation of ␣ 1 adrenergic receptors increases the excitability of PVN presympathetic neurons primarily through augmentation of glutamatergic tone and attenuation of GABAergic inputs.

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Section: Retrograde Labeling Of Spinally Projecting Pvn Neuronsmentioning

confidence: 99%

Presynaptic α₁ Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Chen

Li²,

Pan³

2005

J Pharmacol Exp Ther

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“…We suggest that the reason for the disparity in effects of terazosin and doxazosin on mean arterial pressure is the different receptor specificities of the two α 1 ‐adrenoceptor antagonists 14 . In addition to affinity for the α 1 ‐adrenoceptor, terazosin also demonstrates significant binding at the α 2B ‐adrenoceptor, albeit with weaker affinity 7,8 . In contrast, doxazosin shows no affinity for the α 2B ‐adrenoceptor 14 .…”

Section: Discussionmentioning

confidence: 91%

“…These investigators postulated that this reduction in adult blood pressure by preweaning α 1 ‐adrenoceptor blockade could be due to a reduction in vascular smooth muscle hypertrophy and hyperplasia 1 . However, terazosin also demonstrates significant binding at the α 2 ‐adrenoceptor 7,8 . Accordingly, we have used doxazosin, a selective α 1 ‐adrenoceptor antagonist, from postnatal day 1 to 21 to further determine the specific role of the receptor in the development of hypertension and cardiovascular hypertrophy in the SHR.…”

Section: Introductionmentioning

confidence: 99%

Effects of preweaning doxazosin treatment on adult pressure in the spontaneously hypertensive rat

Boesen

Lewis

Kett

et al. 2003

Clin Exp Pharma Physio

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1. The neonatal/preweaning period appears to represent a critical period of involvement of the sympathetic nervous system in the development of hypertension in spontaneously hypertensive rats (SHR). 2. We tested whether alpha1-adrenoceptor-mediated effects during the preweaning period are involved in the development of hypertension in the adult SHR. 3. Male SHR were treated with the alpha1-adrenoceptor antagonist doxazosin (10 mg/kg per day, s.c.) from postnatal day 1 to 21 inclusive. Direct conscious blood pressure and heart rate were measured via the caudal artery at 12 weeks of age. 4. Preweaning treatment with doxazosin had no significant effect on mean arterial blood pressure or heart rate in male SHR at 12 weeks of age. 5. These findings do not support the involvement of alpha1-adrenoceptor-mediated effects during the preweaning period in the development of hypertension in adult SHR.

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“…This may indicate a general dependence on ␣-receptors. However, one has to take into consideration that prazosin is not completely selective in the mouse (17,24).…”

Section: Discussionmentioning

confidence: 99%

Adenosine triphosphate increases the reactivity of the afferent arteriole to low concentrations of norepinephrine

Hultström¹,

Lai²,

Ma³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Adenosine triphosphate (ATP) and norepinephrine (NE) interact in the control of blood flow in the kidney. A combined effect of NE and ATP has not been previously investigated at the level of the afferent arteriole (Af). We studied the effects of ATP on the contractile response of the Af to NE. Vascular reactivity to ATP, NE, and their combination was investigated in isolated perfused Af from mice. The roles of alpha-adrenoceptors and P2-ATP-receptors were investigated by use of specific agonists and antagonists. Cytosolic calcium was measured using the fluorescent calcium dye fura-2. ATP in concentrations from 10(-12) to 10(-4) mol/l induced transient contractions. NE constricted the Af in a dose-dependent manner and induced significant contractions at > 10(-7) mol/l. Treatment with ATP (10(-8) and 10(-6) mol/l) increased the NE response. Diameters were reduced by 20% already at 10(-11) mol/l NE during ATP treatment of 10(-6) mol/l. ATP increased the calcium response to NE significantly at 10(-8) and 10(-7)mol/l NE. The P2-type ATP receptor blocker pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (10(-5) mol/l) abolished the sensitization of the NE response by ATP. The alpha(1)-blocker prazosin (10(-7) mol/l) inhibited the ATP effect, as did the alpha 2-blocker yohimbine (10(-7) mol/l). Neither the phenylephrine- nor clonidine-induced concentration response curves was affected by ATP in the bath solution. Costimulation with ATP enhances the response of the Af to NE. This effect is mediated by increased cytosolic calcium. The enhancing effect involves P2-type ATP receptors and both alpha (1)- and alpha 2-adrenoceptors.

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[3H]R-Terazosin binds selectively to α1-adrenoceptors over α2-adrenoceptors – comparison with racemic [3H]terazosin and [3H]prazosin

Cited by 13 publications

References 19 publications

Presynaptic α₁ Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Presynaptic α₁ Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Effects of preweaning doxazosin treatment on adult pressure in the spontaneously hypertensive rat

Adenosine triphosphate increases the reactivity of the afferent arteriole to low concentrations of norepinephrine

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[3H]R-Terazosin binds selectively to α1-adrenoceptors over α2-adrenoceptors – comparison with racemic [3H]terazosin and [3H]prazosin

Cited by 13 publications

References 19 publications

Presynaptic α1 Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Presynaptic α1 Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Effects of preweaning doxazosin treatment on adult pressure in the spontaneously hypertensive rat

Adenosine triphosphate increases the reactivity of the afferent arteriole to low concentrations of norepinephrine

Contact Info

Product

Resources

About

Presynaptic α₁ Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons

Presynaptic α₁ Adrenergic Receptors Differentially Regulate Synaptic Glutamate and GABA Release to Hypothalamic Presympathetic Neurons