Evidence for the involvement of α1-adrenoceptors in negative feedback regulation of noradrenergic transmitter release in rat atria

1985 ◽  
Vol 68 (s10) ◽  
pp. 111s-115s ◽  
Author(s):  
D. F. Story ◽  
C. A. Standford-Starr ◽  
M. J. Rand
Keyword(s):  
Transmitter Release ◽  
Feedback Regulation ◽  
Sympathetic Nerves ◽  
Field Stimulation ◽  
Negative Feedback Regulation ◽  
Rat Atria ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Isolated Atria ◽  
Stimulation Of

1. Experiments were undertaken to determine if prejunctional α1-adrenoceptors are involved in autoinhibitory regulation of transmitter noradrenaline release in rat atria. 2. The noradrenergic transmitter stores in rat isolated atria were radiolabeled with [3H]noradrenaline and transmitter release was deduced from the efflux of the radiolabel evoked by field stimulation of the atrial intramural sympathetic nerves. 3. Phentolamine (3 μmol/l) and prazosin (0.1 and 3 μmol/l) enhanced the release of radiolabel evoked by stimulation with trains of 4, 8 and 16 pulses, whereas idazoxan (10 μmol/l) enhanced release evoked by stimulation with 8 and 16 pulses. Idazoxan and prazosin were about equieffective in enhancing the evoked release but phentolamine produced much greater enhancement than either idazoxan or prazosin. 4. Combination of idazoxan (10 μmol/l) and prazosin enhanced the stimulation-evoked release with 4, 8 and 16 pulses to the same extent as phentolamine (3 μmol/l). 5. The selective α1-adrenoceptor agonist methoxamine (10 μmol/l) inhibited stimulation-evoked release and this effect was blocked by the α1-adrenoceptor antagonist prazosin (0.1 μmol/l). 6. The findings indicate that α1-adrenoceptors may contribute to autoinhibitory feedback regulation of transmitter release in rat atria.

Evidence that transmitter release in sympathetic nerves is not set by feedback via presynaptic receptors

1983 ◽  
Vol 61 (10) ◽  
pp. 1197-1201 ◽  
Author(s):  
Stanley Kalsner
Keyword(s):  
Guinea Pig ◽  
Negative Feedback ◽  
Noradrenaline Release ◽  
Transmitter Release ◽  
Feedback Regulation ◽  
Feedback System ◽  
Sympathetic Nerves ◽  
Presynaptic Receptors ◽  
Negative Feedback Regulation

The possibility of negative feedback regulation of noradrenaline release was studied in the sympathetically innervated ureters of the guinea pig mounted in vitro. Tissues were transmurally stimulated with 300 pulses at 2 Hz over a range of voltages, from 10 to 60 V. It was determined that the output of transmitter increased with increasing voltage but that the effects of supposed presynaptic antagonism by yohimbine and presynaptic agonism by added noradrenaline did not fulfill the requirements of presynaptic theory governing negative feedback. It is concluded that the presynaptic effects of these drugs is neither linked to the operation of a negative feedback system nor sensitive to the perineuronal concentrations of free and active neurotransmitter.

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.

Structural and functional study of control of canine tracheal smooth muscle

1980 ◽  
Vol 238 (1) ◽  
pp. C27-C33 ◽  
Author(s):  
M. S. Kannan ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Sympathetic Nerves ◽  
Tracheal Smooth Muscle ◽  
Functional Study ◽  
Field Stimulation ◽  
Electron Microscopic ◽  
Microscopic Studies ◽  
Stimulation Of

The structural bases for myogenic and neurogenic control of canine tracheal smooth muscle were studied. At optimum lengths, strips of muscle showed insignificant neurogenic or myogenic tone. Atropine and/or tetrodotoxin blocked the contractile responses elicited on electrical field stimulation of intrinsic nerves. After raising the tone with tetraethylammonium ion and in the presence of atropine, field stimulation of nerves caused a relaxation, a major component of which was blocked by propranolol and/or tetrodotoxin, suggesting an effect mediated through interaction of mediator released from sympathetic nerves with beta-adrenergic receptors. Electron microscopic studies revealed gap junctions between extensions of smooth-muscle cells and a sparse innervation. The axonal varicosities, corresponding to cholinergic (predominantly) and adrenergic (occasionally) nerves, were seen predominantly in the clefts between cell bundles. The physiological responses were compared with the morphological features. Although this muscle exhibits multiunit behavior in vitro, implying that nerves initiate the coordinate activity, its ultrastructural features suggest a potential for single-unit behavior.

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.

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.

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.

Effects of histamine on rat isolated atria

1980 ◽  
Vol 58 (9) ◽  
pp. 1114-1116 ◽  
Author(s):  
I. Laher ◽  
J. H. McNeill
Keyword(s):  
Muscarinic Receptors ◽  
Right Atrium ◽  
Inotropic Response ◽  
Chronotropic Response ◽  
Adrenoceptor Antagonist ◽  
Endogenous Noradrenaline ◽  
Isolated Atria ◽  
High Doses ◽  
Indirect Stimulation ◽  
Stimulation Of

The effects of histamine were studied in atria obtained from untreated and reserpine-pretreated rats. At high doses, histamine caused a positive chronotropic response that was not antagonized by either promethazine or cimetidine. In the presence of propranolol or in atria from reserpine-pretreated rats histamine caused an atropine-sensitive negative chronotropic response. Large doses of histamine also caused a positive inotropic response in left atria that were antagonized by the β adrenoceptor antagonist propranolol. Reserpine pretreatment abolished the inotropic response of histamine in the rat heart. The results indicate that in large doses histamine causes an indirect stimulation of β adrenoceptors (right and left atrium) by releasing endogenous noradrenaline and of muscarinic receptors (right atrium) by releasing acetylcholine.

Facilitatory β2-adrenoceptors on cholinergic and adrenergic nerve endings of the guinea pig trachea

1999 ◽  
Vol 276 (3) ◽  
pp. L420-L425 ◽  
Author(s):  
Jan Roelof A. de Haas ◽  
J. Saskia Terpstra ◽  
Monica van der Zwaag ◽  
Pieter G. E. Kockelbergh ◽  
Ad F. Roffel ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Time Profile ◽  
Adrenergic Nerve ◽  
Field Stimulation ◽  
Electrical Field ◽  
Control Value ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenergic Nerve Endings

Using electrical field stimulation of epithelium-denuded intact guinea pig tracheal tube preparations, we studied the presence and role of prejunctional β2-adrenoceptors by measuring evoked endogenous acetylcholine (ACh) and norepinephrine (NE) release directly. Analysis of ACh and NE was through two HPLC systems with electrochemical detection. Electrical field stimulation (150 mA, 0.8 ms, 16 Hz, 5 min, biphasic pulses) released 29.1 ± 2.5 pmol ACh/g tissue and 70.2 ± 6.2 pmol NE/g tissue. Preincubation for 15 min with the selective β2-adrenoceptor agonist fenoterol (1 μM) increased both ACh and NE overflow to 178 ± 28 ( P < 0.01) and 165 ± 12% ( P < 0.01), respectively, of control values, increases that were abolished completely by the selective β2-adrenoceptor antagonist ICI-118551 (1 μM). Further experiments with increasing fenoterol concentrations (0.1–100 μM) and different preincubation periods (1, 5, and 15 min) showed a strong and concentration-dependent facilitation of NE release, with maximum response levels decreasing (from nearly 5-fold to only 2.5-fold of control value) with increasing agonist contact time. In contrast, sensitivity of facilitatory β2-adrenoceptors on cholinergic nerves to fenoterol gradually increased when the incubation period was prolonged; in addition, a bell-shaped concentration-response relationship was found at 15 min of preincubation. Fenoterol concentration-response relationships (15-min agonist preincubation) in the presence of atropine and yohimbine (1 μM each) were similar in the case of NE release, but in the case of ACh release, the bell shape was lost. The results indicate a differential capacity and response time profile of facilitatory prejunctional β2-adrenoceptors on adrenergic and cholinergic nerve terminals in the guinea pig trachea and suggest that the receptors on adrenergic nerves are more susceptible to desensitization.

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