Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids.

To characterize the beta-adrenergic receptors on guinea pig gastric smooth muscle cells, we examined the effects of beta-adrenergic agonists and antagonists on biological activity, cellular adenosine 3',5'-cyclic monophosphate (cAMP), and radioligand binding. Adrenergic agonists, isoproterenol (ISO), epinephrine (EPI), and norepinephrine (NE), inhibited carbachol-stimulated contraction of muscle cells, with relative potencies (IC50S) of ISO (0.1 microM) greater than EPI (1.4 microM) greater than NE (11 microM). Each agonist increased cellular cAMP, with relative potencies (IC50S) of ISO (0.5 microM) greater than EPI (6.3 microM) greater than NE (56 microM). Binding of the nonselective beta-antagonist 125I-pindolol was temperature-dependent, saturable, reversible, and specific. 125I-pindolol binding was inhibited by the three agonists, with relative potencies (IC50S) of ISO (0.9 microM) greater than EPI (9.6 microM) greater than NE (112 microM). Pindolol inhibited binding of 125I-pindolol with an IC50 of 100 nM. The IC50 for inhibition of binding of 125I-pindolol by the relatively beta 2-selective antagonist ICI 118,551 was 70 nM and for the relatively beta 1-selective antagonist betaxolol was 1,000 nM. Computer analysis of the dose-inhibition curves for binding of 125I-pindolol for the antagonists indicated that gastric smooth muscle cells possess exclusively beta 2-adrenergic receptors of two classes, one class with a high affinity for ICI 118,551 (Kd = 50 nM) and the other with a low affinity for ICI 118,551 (Kd = 30 microM). Our results indicate that beta-adrenergic agonists interact with beta 2-adrenergic receptors on gastric smooth muscle cells to increase cellular cAMP and inhibit muscle contraction.

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Beta-adrenergic actions on membrane electrical properties of dissociated smooth muscle cells

AJP Cell Physiology ◽

10.1152/ajpcell.1988.254.3.c423 ◽

1988 ◽

Vol 254 (3) ◽

pp. C423-C431 ◽

Cited By ~ 9

Author(s):

H. Yamaguchi ◽

T. W. Honeyman ◽

F. S. Fay

Keyword(s):

Smooth Muscle ◽

Membrane Potential ◽

Electrical Properties ◽

Smooth Muscle Cells ◽

Input Resistance ◽

Muscle Cells ◽

Resting Potential ◽

Equilibrium Potential ◽

Dependent Manner ◽

Beta Adrenergic

Studies were carried out to determine the effects of the beta-adrenergic agent, isoproterenol (ISO), on membrane electrical properties in single smooth muscle cells enzymatically dispersed from toad stomach. In cells bathed in buffer of physiological composition, the average resting potential was -56.4 +/- 1.4 mV (mean +/- SE, n = 35). The dominant effect of exposure to ISO was hyperpolarization. The hyperpolarization was apparent in all cells studied and averaged 11.6 +/- 1.2 mV (n = 27). In the majority of the cells, hyperpolarization was accompanied by a decreased input resistance (Rin). Often the change in resistance appeared to lag behind the change in membrane potential. The lack of coincident changes in membrane potential and resistance may reflect a superposition of the outward rectification properties of the membrane on beta-adrenergic-induced increases in ionic conductance. In about half of the cells, an initial small depolarization (3.1 +/- 0.3 mV, n = 14) was accompanied by a small but distinct increase in Rin (12 +/- 2.5%). When membrane potential was made more negative than the estimated equilibrium potential for K+ (EK) by injection of current, ISO also produced biphasic effects, an initial hyperpolarization which reversed to a sustained depolarization to a value (-90 mV) near the estimated EK. The hyperpolarization by ISO could be diminished in a time-dependent manner by previous exposure to ouabain. The inhibition by ouabain, however, appeared to be a fortuitous result of glycoside-induced positive shifts in EK. These observations indicate that the dominant electrophysiological effect of beta-adrenergic stimuli is to hyperpolarize the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

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Serotonin, histamine, and norepinephrine mediation of endothelial and vascular smooth muscle cell movement

AJP Cell Physiology ◽

10.1152/ajpcell.1985.248.3.c252 ◽

1985 ◽

Vol 248 (3) ◽

pp. C252-C257 ◽

Cited By ~ 46

Author(s):

D. Bottaro ◽

D. Shepro ◽

S. Peterson ◽

H. B. Hechtman

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Vascular Smooth Muscle Cell ◽

Adrenergic Receptors ◽

Cell Movement ◽

Bovine Aortic Endothelial Cell ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic

The effects of serotonin (5-HT), histamine (H), and norepinephrine (NE) on bovine aortic endothelial cell (BAE) and vascular smooth muscle cell (VSM) movement were quantitated using a phagokinetic tracking assay. BAE movement was significantly reduced by 5-HT (31%), H (48%), and NE (62%) at concentrations ranging from 10(-10) to 10(-4) M (P less than 0.01). VSM motility was significantly enhanced by 5-HT (17%) and H (25%) at concentrations of 10(-8) and 10(-4)M, respectively (P less than 0.01). NE (10(-4)M) reduced VSM motility by 63% (P less than 0.01). Ketanserin (1 microM) reduced the 5-HT-associated inhibition of BAE movement by 75% (P less than 0.01). Diphenhydramine (1 microM) reduced the H-associated inhibition of BAE movement by 66% (P less than 0.01). Propranolol (1 microM) reduced NE-associated inhibition of BAE movement by 50% (P less than 0.01) and 5-HT-associated inhibition by 45% (P less than 0.05), but phenoxybenzamine had no significant effect. The results suggest 1) BAE and VSM are affected qualitatively in opposite ways by 5-HT and H; 2) the H-associated inhibition of BAE movement appears to be at least partially mediated by H1 receptors; 3) the 5-HT-associated inhibition of BAE movement may be mediated directly by a 5-HT binding component but indirectly by beta-adrenergic receptors; and 4) the NE-associated inhibition of BAE movement appears to be mediated by beta-adrenergic receptors.

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α2-Adrenergic receptors increase cell migration and decrease F-actin labeling in rat aortic smooth muscle cells

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.3.c654 ◽

1998 ◽

Vol 274 (3) ◽

pp. C654-C662 ◽

Cited By ~ 47

Author(s):

Jeremy G. Richman ◽

John W. Regan

Keyword(s):

Wound Healing ◽

Smooth Muscle ◽

Cell Migration ◽

Smooth Muscle Cells ◽

Adrenergic Receptors ◽

Muscle Cells ◽

Mitogen Activated Protein Kinase ◽

Protein Kinase Activity ◽

Promote Cell Proliferation ◽

Aortic Smooth Muscle

Vascular wound healing and such pathologies as atherosclerosis and restenosis are characterized by migration and proliferation of the smooth muscle cells of the media after denudation of the intima. To explore possible roles that α2-adrenergic receptors (α2-ARs) might have in these cellular responses, we characterized the α2-ARs present in explant-derived cultures of rat aortic smooth muscle (RASM) cells. The results of immunofluorescence microscopy and reverse transcription followed by the polymerase chain reaction indicated that all three α2-AR subtypes (α2A, α2B, and α2C) were initially present. Mitogen-activated protein kinase activity in the RASM cells was stimulated fivefold over basal by the α2-selective agonist dexmedetomidine (Dex) and was blocked by coincubation with the α2-selective antagonist rauwolscine (RW) or by preincubation of the cells with the Gi/Go-protein inhibitor pertussis toxin. α2-AR activation by Dex did not promote cell proliferation, as measured by the incorporation of [3H]thymidine. However, Dex significantly increased RASM cell migration, and antagonist blocked this effect. Incubation of RASM cells with Dex also produced a marked decrease in F-actin labeling, which again was prevented by coincubation with RW. The evidence clearly reveals the presence of functional α2-ARs in RASM cells. The involvement of α2-AR activation with cytoskeletal changes and cell migration is novel and indicates a potential role of these receptors in vascular wound healing and pathogenesis.

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Norepinephrine-induced down regulation of alpha1 adrenergic receptors in cultured rabbit aorta smooth muscle cells

Life Sciences ◽

10.1016/0024-3205(83)90824-x ◽

1983 ◽

Vol 33 (14) ◽

pp. 1409-1417 ◽

Cited By ~ 42

Author(s):

J.E.S. Wikberg ◽

M. Akers ◽

M.G. Caron ◽

P-O. Hagen

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Adrenergic Receptors ◽

Rabbit Aorta ◽

Muscle Cells ◽

Down Regulation

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Noradrenergic inhibitory innervation of canine airways

Journal of Applied Physiology ◽

10.1152/jappl.1980.48.1.16 ◽

1980 ◽

Vol 48 (1) ◽

pp. 16-22 ◽

Cited By ~ 34

Author(s):

J. A. Russell

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Adrenergic Receptors ◽

Electric Stimulation ◽

Neural Mechanism ◽

Inhibitory Response ◽

Sympathetic System ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic ◽

Resting Tone

The inhibitory innervation of canine airways was examined in isolated trachealis strips and helical strips of airways having outside diameters of 5 and 1.5 mm. Exogenous norepinephrine (10-8 M to 10-3 M) did not alter resting tone but relaxed airways contracted by 10-5 M histamine. Relaxations produced by norepinephrine were antagonized by 10-6 M propranolol, demonstrating the presence of beta-adrenergic receptors. Trans-ural electric stimulation also inhibited contractions produced by histamine. These electrically induced relaxations were blocked by tetrodotoxin and were reduced in magnitude by propranolol, indicating the involvement of a sympathetic neural mechanism. The inhibitory response to electric stimulation was attenuated in airways from catecholamine-depleted dogs and abolished in four of nine catecholamine-depleted airways pretreated with propranolol. Exogenous tyramine (10-5 M) also relaxed histamine-induced contractions, and this effect was blocked by propranolol or catecholamine depletion. The study showed that beta-adrenergic receptors from the trachea to 1.5-mm airways are innervated and that this sympathetic system constitutes the primary inhibitory innervation of airway smooth muscle in the dog.

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