scholarly journals Effect of compound D-600 (methoxyverapamil) on gluconeogenesis and on acceleration of the process by α-adrenergic stimuli in rat kidney tubules

1980 ◽  
Vol 190 (2) ◽  
pp. 283-291 ◽  
Author(s):  
E D Saggerson ◽  
C A Carpenter
Keyword(s):  
Renal Cortex ◽  
Rat Kidney ◽  
Sodium Lactate ◽  
Kidney Tubules ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Blocker ◽  
Glucose Formation ◽  
Stimulation Of

1. Tubule fragments were isolated from renal cortex of fed rats and glucose formation was measured after incubation with 5 mM-sodium lactate. 20 Compound D-600 (10-100 microM) decreased gluconeogenesis from lactate. This inhibition of the process by compound D-600 increased with increasing extracellular Ca2+ concentration, was overridden by noradrenaline and diminished by starvation for 24 h. 3. Inhibition of lactate-supported gluconeogenesis by compound D-600 was not prevented by the alpha 1-adrenoceptor antagonist thymoxamine. 4. Compound D-600 had little effect on gluconeogenesis from 2-oxoglutarate and increased gluconeogenesis from succinate. 5. Compound D-600 opposed stimulation of gluconeogenesis by noradrenaline or oxymetazoline (a selective alpha-adrenoceptor agonist) in a manner suggesting that compound D-600 is an alpha-adrenoceptor blocker. Oxymetazoline was more sensitive than noradrenaline to blockade by both compound D-600 and by the conventional alpha-adrenoceptor antagonist phentolamine. Noradrenaline became more sensitive to blockade by compound D-600 when extracellular Ca2+ was decreased. 6. Compound D-600 did not block stimulation of gluconeogenesis by angiotensin or cyclic AMP.

Effect of stimulation of nucleus raphe dorsalis on carotid blood flow. II. The cat

1985 ◽  
Vol 248 (2) ◽  
pp. R263-R269 ◽  
Author(s):  
P. J. Goadsby ◽  
R. D. Piper ◽  
G. A. Lambert ◽  
J. W. Lance
Keyword(s):  
Intravenous Administration ◽  
Spinal Cord Section ◽  
Homocysteic Acid ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Blocker ◽  
Raphe Dorsalis ◽  
Constrictor Response ◽  
The Brain ◽  
Stimulation Of

The dorsal raphe nucleus (DRN) and surrounding midbrain of 74 cats were stimulated both electrically and chemically, and carotid flows were measured with electromagnetic flow probes. Stimulation of the DRN caused a frequency-dependent decrease in common carotid vascular resistance, which was abolished by bilateral section of the facial nerve intracranially. Injection of DL-homocysteic acid into the DRN reproduced the effect of electrical stimulation, indicating that the responses arose from excitation of cell bodies within the DRN, not from fibers of passage. The responses were mediated entirely within the brain stem since they remained intact after high spinal cord section. The vasodilator response was blocked by the intravenous administration of the nicotinic ganglion blocker hexamethonium but not by the alpha-adrenoceptor blocker phentolamine. The responses were unaffected by intravenous administration of methysergide but were markedly reduced after depletion of central serotonin by pretreatment with the serotonin depletor, p-chlorophenylalanine. A poststimulus constrictor response was mediated by release of catecholamines from the adrenal medulla and was blocked by the alpha-adrenoceptor antagonist phentolamine. No response involved supracollicular mechanisms since they persisted after decerebration.

scholarly journals Evidence that catecholamines stimulate renal gluconeogenesis through an α1-type of adrenoceptor

1980 ◽  
Vol 190 (1) ◽  
pp. 119-123 ◽  
Author(s):  
P Kessar ◽  
E D Saggerson
Keyword(s):  
Rat Kidney ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Renal Gluconeogenesis ◽  
Adrenoceptor Agonist ◽  
Alpha Agonist

1. Noradrenaline stimulates gluconeogenesis through an alpha-adrenoceptor in renal cortical tubule fragments from fed rats incubated with 5 mM-lactate. 2. The selective alpha 1-adrenoreceptor agonist methoxamine stimulated gluconeogenesis, but the selective alpha 2-adrenoceptor agonist clonidine was ineffective. 3. The selective alpha 1-adrenoceptor antagonist thymoxamine blocked the stimulatory effects on gluconeogenesis of noradrenaline and of oxymetazoline (a synthetic alpha-agonist). The selective alpha 2-adrenoceptor antagonist yohimbine was ineffective in this respect. 4. It is concluded that noradrenaline and oxymetazoline stimulate gluconeogenesis in rat kidney via an alpha 1-rather than an alpha 2-type of adrenoceptor.

Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

2009 ◽  
Vol 296 (4) ◽  
pp. C766-C782 ◽  
Author(s):  
Sharon Tsang ◽  
Stanley S. C. Wong ◽  
Song Wu ◽  
Gennadi M. Kravtsov ◽  
Tak-Ming Wong
Keyword(s):  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Contractile Responses ◽  
Adrenoceptor Antagonist ◽  
Cardiac Contractile ◽  
Plasmic Reticulum ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Developed Pressure ◽  
Stimulation Of

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10−7 M), the α1-adrenoceptor agonist phenylephrine (10−6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10−7 M) in the presence of 5 × 10−7 M ICI-118,551, a β2-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX.

scholarly journals Catecholamines modulate podocyte function.

1998 ◽  
Vol 9 (3) ◽  
pp. 335-345 ◽  
Author(s):  
T B Huber ◽  
J Gloy ◽  
A Henger ◽  
P Schollmeyer ◽  
R Greger ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Patch Clamp Technique ◽  
Extracellular Solution ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists ◽  
Beta 2 ◽  
Cl Conductance ◽  
Stimulation Of ◽  
Ion Conductances

The aim of this study was to investigate the influence of adrenoceptor agonists on the intracellular calcium activity ([Ca2+]i), membrane voltage (Vm), and ion conductances (Gm) in differentiated mouse podocytes. [Ca2+]i was measured by the Fura-2 fluorescence method in single podocytes. Noradrenaline and the alpha 1-adrenoceptor agonist phenylephrine induced a reversible and concentration-dependent biphasic increase of [Ca2+]i in podocytes (EC50 approximately 0.1 microM for peak and plateau), whereas the alpha 2-adrenoceptor agonist UK 14.304 did not influence [Ca2+]i. The [Ca2+]i response induced by noradrenaline was completely inhibited by the alpha 1-adrenoceptor antagonist prazosin (10 nM). In a solution with a high extracellular K+ (72.5 mM), [Ca2+]i was unchanged and the [Ca2+]i increase induced by noradrenaline was not inhibited by the L-type Ca2+ channel blocker nicardipine (1 microM). Vm and Gm were examined with the patch-clamp technique in the slow whole-cell configuration. Isoproterenol, phenylephrine, and noradrenaline depolarized podocytes and increased Gm. The order of potency for the adrenoceptor agonists was isoproterenol (EC50 approximately 1 nM) > noradrenaline (EC50 approximately 0.3 microM) > phenylephrine (EC50 approximately 0.5 microM). The beta 2-adrenoceptor antagonist ICI 118.551 (5 to 100 nM) inhibited the effect of isoproterenol on Vm. Stimulation of adenylate cyclase by forskolin mimicked the effect of isoproterenol on Vm and Gm (EC50 approximately 40 nM). Isoproterenol induced a time- and concentration-dependent increase of cAMP in podocytes. The effect of isoproterenol was unchanged in the absence of Na+ or in an extracellular solution with a reduced Ca2+ concentration, whereas it was significantly increased in an extracellular solution with a reduced Cl- concentration (from 145 to 32 mM). The data indicate that adrenoceptor agonists regulate podocyte function: They increase [Ca2+]i via an alpha 1-adrenoceptor and induce a depolarization via a beta 2-adrenoceptor. The depolarization is probably due to an opening of a cAMP-dependent Cl- conductance.

Effect of stimulation of nucleus raphe dorsalis on carotid blood flow. I. The monkey

1985 ◽  
Vol 248 (2) ◽  
pp. R257-R262 ◽  
Author(s):  
P. J. Goadsby ◽  
R. D. Piper ◽  
G. A. Lambert ◽  
J. W. Lance
Keyword(s):  
Facial Nerve ◽  
External Carotid ◽  
Blood Flows ◽  
Beta Adrenoceptor ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Muscarinic Cholinergic ◽  
Raphe Dorsalis ◽  
Carotid Circulation ◽  
Stimulation Of

The dorsal raphe nucleus (DRN) and surrounding midbrain of 16 anaesthetized monkeys were stimulated electrically, and carotid blood flows were measured with electromagnetic flow probes. Stimulation of the DRN caused a frequency-dependent decrease (vasodilatation) in both internal and external carotid vascular resistance, which was abolished in both circulations by bilateral section of the facial nerve intracranially. These vasodilator responses were unaltered by intravenous administration of muscarinic cholinergic or by alpha- or beta-adrenoceptor antagonists. A postdilatation constrictor response, observed in the external carotid circulation, was blocked by the alpha-adrenoceptor antagonist phentolamine. It is concluded that projections of the DRN through the greater superficial petrosal branch of the facial nerve mediate vasodilatation in both internal and external carotid circulations.

Evidence for existence of postjunctional alpha 1- and alpha 2-adrenoceptors in cat pulmonary vascular bed

1985 ◽  
Vol 249 (4) ◽  
pp. H891-H898
Author(s):  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Adrenergic Nerve ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Vascular Bed ◽  
Alpha Adrenoceptor Agonists ◽  
Adrenoceptor Blocker ◽  
Adrenoceptor Agonists ◽  
Uk 14,304 ◽  
6 Hydroxydopamine ◽  
Pulmonary Vascular Bed

The subtypes of postjunctional alpha-adrenoceptors in the feline pulmonary vascular bed were studied using selective alpha-adrenoceptor agonists and antagonists. Under conditions of controlled pulmonary blood flow and constant left atrial pressure, intralobar injections of the alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, and the alpha 2-adrenoceptor agonists, UK 14,304 and BHT 933, increased lobar arterial pressure in a dose-related manner. Prazosin, an alpha 1-adrenoceptor antagonist, reduced responses to phenylephrine and methoxamine to a greater extent than responses to UK 14,304 and BHT 933. Yohimbine, an alpha 2-adrenoceptor blocker, decreased responses to UK 14,304 and BHT 933 without altering responses to phenylephrine or methoxamine. The same pattern of blockade was observed in animals pretreated with 6-hydroxydopamine, an agent that destroys the integrity of adrenergic nerve terminals. However, in propranolol-treated animals, prazosin antagonized responses to phenylephrine and methoxamine without altering responses to UK 14,304 or BHT 933, and the selectivity of the blocking effects of yohimbine were preserved. Responses to intralobar injections of norepinephrine were markedly decreased by prazosin, whereas yohimbine had only a small effect. These data suggest the presence of both postjunctional alpha 1- and alpha 2-adrenoceptors mediating vasoconstriction in the pulmonary vascular bed. These results also indicate that the vasoconstrictor responses to injected norepinephrine in the cat pulmonary vascular bed are due mainly to activation of alpha 1-adrenoceptors.

Ontogeny of alpha-adrenoceptor responses in renal vascular bed of sheep

1988 ◽  
Vol 254 (2) ◽  
pp. R277-R283 ◽  
Author(s):  
G. P. Matherne ◽  
K. T. Nakamura ◽  
J. E. Robillard
Keyword(s):  
Renal Vasoconstriction ◽  
Adult Sheep ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Low Concentrations ◽  
Adrenoceptor Agonist ◽  
Similar Dose ◽  
Nonpregnant Adult ◽  
Phenylephrine Infusion ◽  
Renal Vascular

The renal hemodynamic response to renal arterial infusions of guanabenz (alpha 2-adrenoceptor agonist) and phenylephrine (alpha 1-adrenoceptor agonist) were compared in conscious and chronically instrumented fetal (132-140 days gestation; term 145 days), newborn (6-15 days postnatal), and nonpregnant adult sheep. Phenylephrine produced similar dose-related decreases in renal blood flow velocity in all three groups at low concentrations (less than 1.8 X 10(-7) M) of drug in renal blood, whereas at the highest concentration adults demonstrated the most vasoconstriction and newborns the least (P less than 0.05 ANOVA). Responses to phenylephrine infusion during renal alpha 1-adrenoceptor blockade with prazosin were completely inhibited. Guanabenz produced greater renal vasoconstriction in adult sheep (P less than 0.05 ANOVA) at all concentrations (0.6 X 10(-6) to 8 X 10(-6) M) when compared with fetal and newborn sheep. Guanabenz-mediated vasoconstriction was not affected by alpha 1-adrenoceptor blockade with prazosin but was completely inhibited by the addition of an alpha 2-adrenoceptor antagonist idazoxan. Results of the present study demonstrate that renal vasoconstriction is mediated by both alpha 1- and alpha 2-adrenoceptors in fetal, newborn, and adult sheep. Moreover, these results suggest that renal alpha 1- and alpha 2-adrenoceptor-mediated vasoconstrictor responses mature at different rates.

Nerve-induced nonadrenergic vasoconstriction and vasodilatation in skeletal muscle

1990 ◽  
Vol 258 (5) ◽  
pp. H1334-H1338 ◽  
Author(s):  
A. Ohlen ◽  
M. G. Persson ◽  
L. Lindbom ◽  
L. E. Gustafsson ◽  
P. Hedqvist
Keyword(s):  
High Frequency ◽  
Motor Nerve ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Stimulation Parameters ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation ◽  
Stimulation Of

Intravital microscopy was used to study the effect of motor nerve stimulation on microvessel diameters in the rabbit tenuissimus muscle. Stimulation of the motor nerve (0.5-5 ms, 2-20 Hz, 5-15 V) evoked pulse duration- and frequency-dependent constriction of transverse and terminal arterioles. The vasoconstriction induced by low-frequency stimulation (2 Hz) was abolished by the alpha-adrenoceptor antagonist phentolamine, whereas high-frequency stimulation (10-20 Hz) resulted in a response that was only partially inhibited by phentolamine. However, desensitization of the tissue to the vasoconstrictor effects of neuropeptide Y (NPY) changed the response remaining after phentolamine into vasodilatation. Independent of stimulation parameters, pretreatment of the tissue with the adrenergic neuron blocker guanethidine reversed the constriction into dilatation that was resistant to propranolol, atropine, and indomethacin. The results document the functional presence of both vasoconstrictor and vasodilator fibers in the rabbit tenuissimus muscle motor nerve, and they suggest that part of the nerve-induced vasoconstriction at higher stimulation frequencies is caused by neuronally released NPY.

Effects of alpha-adrenergic agonists on intracellular and intramitochondrial pH in rat proximal nephrons

1989 ◽  
Vol 257 (4) ◽  
pp. F623-F630 ◽  
Author(s):  
F. A. Gesek ◽  
A. C. Schoolwerth
Keyword(s):  
Specific Inhibitor ◽  
Weak Acid ◽  
Adrenergic Agonists ◽  
Acetoxymethyl Ester ◽  
Maximum Increase ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Agonist ◽  
Proximal Tubular ◽  
Adrenoceptor Agonists ◽  
Stimulation Of

Rat proximal tubular segments were used to examine alpha-adrenoceptor alterations in Na+-H+ exchange by monitoring intracellular pH (pHi) and mitochondrial matrix pH (pHm). To obtain pHi, tubules were incubated with the cell-permeant fluorescent probe, 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein acetoxymethyl ester in a HCO3--free Na+ buffer. The intracellular distribution of the weak acid [2-14C] 5,5-dimethyloxazolidine-2,4-dione was used to calculate pHm, using values of medium pH, pHi, cell volume, and matrix content. Several selective alpha 1- and alpha 2-adrenoceptor agonists and the endogenous mixed agonist, norepinephrine, all produced dose-related increases in pHi. With each of the agonists tested, a maximum increase in pHi was observed at 1 microM final concentrations, with peak effects occurring in less than 1 min. Pretreatment with ethylisopropyl amiloride (EIPA, 10 microM), a specific inhibitor of proximal Na+-H+ exchange, blocked receptor-stimulated increases in pHi, as well as stimulation of Na+-H+ exchange by phorbol ester (PMA, 0.1 microM). Similarly, selective alpha 1- (prazosin, 0.1 microM) and alpha 2-(idazoxan, 0.1 microM) adrenoceptor antagonists inhibited alterations in agonist-induced pHi changes, whereas PMA-stimulated increases in pHi remained unaffected. Neither alpha 1- nor alpha 2-adrenoceptor agonists produced differences in pHm. Adrenoceptor agonist-induced pHi changes were also assessed at various concentrations of external Na+ (0-135 mM). It was observed that 0 and 10 mM external Na+ concentrations significantly reduced alpha 1- and alpha 2-adrenoceptor-stimulated pHi changes; Km values for the alpha 1-agonist phenylephrine and the alpha 2-agonist B-HT 933 were 18.0 +/- 2.1 and 22.7 +/- 2.6, respectively. In summary, stimulation by alpha-adrenergic agonists may be blocked at the receptor level with specific alpha-antagonists or at the exchanger with EIPA. The increase in cellular pH induced by these agonists is sensitive to external Na+ and reflects alpha-adrenoceptor activation of the Na+-H+ exchanger.

Effects of hyperthermia on contraction and dilatation of rabbit femoral arteries

1998 ◽  
Vol 85 (6) ◽  
pp. 2205-2212 ◽  
Author(s):  
Jaime Padilla ◽  
Angel Luis García-Villalón ◽  
Nuria Fernández ◽  
Luis Monge ◽  
Bernardino Gómez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Receptor Antagonist ◽  
Sodium Nitroprusside ◽  
Femoral Artery ◽  
Vascular Response ◽  
Weak Contraction ◽  
Endothelin 1 ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Stimulation Of

To analyze the effect of hyperthermia on the vascular response, the isometric response of isolated rabbit femoral artery segments was recorded at 37°C and hyperthermia (41 and 44°C). Contraction to potassium (5 × 10−3-5 × 10−2 M) was significantly greater at 41 and 44 than at 37°C and increased by inhibition of nitric oxide (NO) synthesis with N ω-nitro-l-arginine (l-NNA; 10−4 M) or endothelium removal at 37°C but not at 41 or 44°C. Norepinephrine (10−9-10−4M) produced a concentration-dependent contraction greater at 41 or 44 than at 37°C and not modified by endothelium removal orl-NNA at either temperature. Phenylephrine (10−9-10−4M) produced a contraction increased by warming to 44°C but not to 41°C. The specific α2-adrenoceptor agonist BHT-920 produced a weak contraction, reduced by the α1-adrenoceptor antagonist prazosin (10−6 M) and increased at 44°C but not at 41°C. The concentration-dependent contraction to endothelin-1 (ET-1; 10−11-10−7M) was increased by warming to 41 and 44°C and by endothelium removal or l-NNA at 37°C but not at 41 or 44°C. Response to ET-1 was reduced by endothelin ETA-receptor antagonist BQ-123 (10−5 M) and ETB-receptor antagonist BQ-788 (10−5 M). In arteries precontracted with ET-1 (10−8-3 × 10−8 M), relaxation to sodium nitroprusside (10−8-10−4M) was increased at 41 and 44°C vs. at 37°C, but that of ACh (10−8-10−4M) or adenosine (10−8-10−4M) was not different at all temperatures studied. Relaxation to ACh, but not adenosine, was reduced similarly byl-NNA at all temperatures studied. These results suggest hyperthermia in muscular arteries may inhibit production of, and increase dilatation to, NO, resulting in unchanged relaxation to ACh and increased constriction to KCl and ET-1, and may increase constriction to stimulation of α1-adrenoceptors by NO-independent mechanisms.

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