Membrane-delimited stimulation of heart cell calcium current by beta-adrenergic signal-transducing Gs protein

1990 ◽  
Vol 259 (1) ◽  
pp. H264-H267 ◽  
Author(s):  
S. Pelzer ◽  
Y. M. Shuba ◽  
T. Asai ◽  
J. Codina ◽  
L. Birnbaumer ◽  
...  
Keyword(s):  
Calcium Current ◽  
Receptor Activation ◽  
Heart Cell ◽  
Ca Channels ◽  
Beta Adrenergic ◽  
Physiological Regulation ◽  
Beta Receptor ◽  
Adrenergic Response ◽  
Gs Protein ◽  
Stimulation Of

A severalfold increase in calcium current (ICa) is a signal feature of the maximal beta-adrenergic response of the heart. It is generally ascribed to enhanced adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphorylation of calcium (Ca) channels after beta-receptor activation of the guanosine nucleotide-binding (G) protein Gs, and Gs activation of the adenylyl cyclase cascade. We blocked phosphorylation pathways in guinea pig cardiomyocytes to unmask other possible ICa-stimulatory modes. In blocked cells, ICa increased by approximately 50% during 1) beta-receptor activation of Gs, 2) intracellular activation of Gs, and 3) intracellular application of preactivated Gs, We conclude that fast, membrane-delimited Gs modulation participates in the physiological regulation of cardiac ICa.

Membrane-Delimited Stimulation of Heart Cell Calcium Current by ß-Adrenergic Signal-Transducing Gs Protein

1992 ◽  
pp. 113-127
Author(s):  
S. Pelzer ◽  
Y. M. Shuba ◽  
L. Birnbaumer ◽  
T. F. McDonald ◽  
D. J. Pelzer
Keyword(s):  
Calcium Current ◽  
Heart Cell ◽  
Cell Calcium ◽  
Gs Protein ◽  
Stimulation Of

CATECHOLAMINE ANTAGONISM TO OXYTOCIN-INDUCED MILK-EJECTION

1971 ◽  
Vol 68 (1_Suppla) ◽  
pp. S5-S38 ◽  
Author(s):  
Helmuth Vorherr
Keyword(s):  
Receptor Blockade ◽  
Milk Ejection ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Beta Receptors ◽  
Alpha Receptors ◽  
Adrenergic Blockers ◽  
Beta Receptor Blockade ◽  
Second Pain ◽  
Stimulation Of

ABSTRACT In lactating rats and rabbits the mode of antagonism of sympathomimetics, angiotensin or pain toward oxytocin-induced milk-ejection was investigated. In rats intra-arterial (intrafemoral) doses of 0.01–0.02 μg or intravenous (iv) doses of 0.1–0.5 μg of either epinephrine, isoproterenol, norepinephrine, angiotensin or 10 μg of phenylephrine injected simultaneously with, or 30 seconds before an oxytocin dose (10 μU intrafemoral, 300 μU iv) greatly inhibited or suppressed the oxytocin response. A 15 second pain stimulus caused moderate inhibition. With alpha-receptor blockade pain, epinephrine, isoproterenol, norepinephrine, phenylephrine and angiotensin inhibition were, respectively, 70%, 75%, 100%, 40%, 0% and 100%. Under beta-receptor blockade the corresponding values were 14%, 40%, 0%, 70%, 100% and 100%; with simultaneous intrafemoral injections neither catecholamine was inhibitory toward oxytocin. In corresponding rabbit experiments approximately 10-fold higher iv drug dosages were applied and similar results were observed. In both species, combined alpha and beta-receptor blockade nearly eliminated the antagonistic actions of sympathomimetics toward oxytocin, whereas angiotensin inhibition persisted unchanged. The results indicate: 1) Mammary myoepithelial cells contain beta-adrenergic receptors but no alpha-receptors; 2) Inhibition of oxytocin-induced milk-ejection by isoproterenol and phenylephrine is meditated through stimulation of myoepithelial beta-receptors (myoepithelial relaxation) and vascular alpha-receptors (vasoconstriction), respectively; 3) Epinephrine and norepinephrine inhibition of milk-ejection is due to stimulation of vascular alpha-receptors and myoepithelial beta-receptors; 4) Angiotensin effects are unrelated to adrenergic receptor mechanisms; 5) Administration of both alpha and beta-adrenergic blockers is desirable for stabilizing the sensitivity of the oxytocin milk-ejection assay preparation against interference from endogenous or exogenous catecholamines; 6) Other than using adrenergic blockers, pharmacologic doses of oxytocin can correct nursing difficulties in animals and man with hyperfunction of the adrenal-sympathetic system.

Compounds that increase cAMP prevent ischemia-reperfusion pulmonary capillary injury

1992 ◽  
Vol 72 (2) ◽  
pp. 492-497 ◽  
Author(s):  
W. K. Adkins ◽  
J. W. Barnard ◽  
S. May ◽  
A. F. Seibert ◽  
J. Haynes ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Vascular Permeability ◽  
Vascular Resistance ◽  
Capillary Permeability ◽  
Ischemia Reperfusion ◽  
Receptor Activation ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Pulmonary Capillary

This study evaluated the physiological effects of compounds that increase adenosine 3′,5′-cyclic monophosphate (cAMP) on changes in pulmonary capillary permeability and vascular resistance induced by ischemia-reperfusion (I-R) in isolated blood-perfused rabbit lungs. cAMP was elevated by 1) beta-adrenergic stimulation with isoproterenol (ISO, 10(-5) M), 2) post-beta-receptor stimulation of adenylate cyclase with forskolin (FSK, 10(-5) M), 3) and dibutyryl cAMP (DBcAMP, 1 mM), a cAMP analogue. Vascular permeability was assessed by determining the capillary filtration coefficient (Kf,c), and capillary pressure was measured using the double occlusion technique. The total, arterial, and venous vascular resistances were calculated from measured pulmonary arterial, venous, and capillary pressures and blood flow. Reperfusion after 2 h of ischemia significantly (P less than 0.05) increased Kf,c (from 0.115 +/- 0.028 to 0.224 +/- 0.040 ml.min-1.cmH2O-1.100 g-1). These I-R-induced changes in capillary permeability were prevented when ISO, FSK, or DBcAMP was added to the perfusate at reperfusion (0.110 +/- 0.022 and 0.103 +/- 0.021, 0.123 +/- 0.029 and 0.164 +/- 0.024, and 0.153 +/- 0.030 and 0.170 +/- 0.027 ml.min-1.cmH2O-1.100 g-1, respectively). I-R significantly increased total, arterial, and venous vascular resistances. These increases in vascular resistance were also blocked by ISO, FSK, and DBcAMP. These data suggest that beta-adrenergic stimulation, post-beta-receptor activation of adenylate cyclase, and DBcAMP prevent the changes in pulmonary vascular permeability and vascular resistances caused by I-R in isolated rabbit lungs through a mechanism involving an increase in intracellular levels of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

scholarly journals Stimulatory effect of beta-adrenergic agonists on ileal L cell secretion and modulation by alpha-adrenergic activation

1999 ◽  
Vol 162 (2) ◽  
pp. 271-278 ◽  
Author(s):  
J Claustre ◽  
S Brechet ◽  
P Plaisancie ◽  
JA Chayvialle ◽  
JC Cuber
Keyword(s):  
Adrenergic Receptors ◽  
Peptide Yy ◽  
Receptor Activation ◽  
Cell Secretion ◽  
Beta Adrenergic ◽  
L Cells ◽  
Peptide Secretion ◽  
Stimulation Of

Postprandial release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L cells results from both nutrient transit in the ileal lumen and neural drive of endocrine cells. The adrenosympathetic system and its effectors have been shown to induce secretion of L cells in vivo or in vitro. Because these transmitters act through three receptors, beta, alpha1, alpha2, coupled to different intracellular pathways, we evaluated the responses of L cells to specific agonists, using the model of isolated vascularly perfused rat ileum. General stimulation of adrenergic receptors with epinephrine (10(-7) M) induced significant GLP-1 and PYY secretions (94+/-38 and 257+/-59 fmol/8 min respectively) which were abolished upon propranolol (10(-7) M) pretreatment and strongly decreased upon infusion with 10(-8) M prazosin. Blockade of alpha2-receptors with idazoxan (10(-8) M) did not alter epinephrine-induced peptide secretion. The beta-adrenergic agonist isoproterenol (10(-6) M) infused for 30 min induced a transient release of GLP-1 and PYY (integrated release over the 8 min of the peak secretion: 38+/-16 and 214+/-69 fmol for GLP-1 and PYY respectively, P<0.05). Because terbutaline but not dobutamine or BRL 37,344 (10(-5) M) induced significant GLP-1 and PYY secretions (135+/-30 and 305+/-39 fmol/8 min respectively), isoproterenol-induced secretions are suggested to result mainly from stimulation of the beta2-isoreceptor type. In contrast, the alpha1-agonist phenylephrine (10(-7) M) did not stimulate peptide release. When co-infused with 10(-6) M or 10(-7) M isoproterenol, 10(-7) M phenylephrine raised GLP-1 release to 174+/-53 and 108+/-28 fmol/8 min respectively (vs 38+/-16 and 35+/-10 fmol/8 min for isoproterenol alone, P<0.05) whereas PYY secretion was not significantly increased. Clonidine (10(-7) M), an alpha2-agonist, induced a moderate and delayed increase of GLP-1 and PYY but abolished the isoproterenol-induced peptide secretion. Our results showed that general stimulation of adrenergic receptors stimulates the secretory activity of ileal endocrine L cells. The net peptide secretion results from the activation of the beta2-isoreceptor type. Additionally, GLP-1 and PYY secretions are positively modulated by alpha1-receptor stimulation and inhibited by alpha2-receptor activation upon beta-receptor occupation.

Molecular and functional identification of beta-adrenergic receptors in distal convoluted tubule cells

1997 ◽  
Vol 272 (6) ◽  
pp. F712-F720 ◽  
Author(s):  
F. A. Gesek ◽  
K. E. White
Keyword(s):  
Adrenergic Receptors ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Beta Adrenergic Receptors ◽  
Functional Responses ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Beta Receptors ◽  
Beta 2 ◽  
Camp Formation

Renal nerve stimulation or circulating catecholamines activate the beta-adrenergic receptors that mediate direct effects on tubular transport. Three subtypes of beta-adrenergic receptors have been characterized: beta 1, beta 2, and beta 3. beta-Adrenergic-receptor effects on Na+ and Ca2+ transport in distal convoluted tubules (DCT) have not been established. The focus of this study was to 1) identify the subtypes of beta-adrenergic receptors in DCT cells and 2) examine functional responses to beta-receptor activation on adenosine 3',5'-cyclic monophosphate (cAMP) formation and Na+ and Ca2+ entry. To determine the subtypes of beta-receptors present, RNA isolated from immortalized mouse DCT cells was reverse transcribed, and the cDNA was amplified using primers designed to reported sequences for beta 1-, beta 2-, and beta 3-receptor subtypes. Products of the appropriate sizes were obtained with beta 1- and beta 2-primers. No product was observed with primers to the beta 3 sequence. Receptor products were confirmed by sequencing and are identical to reported mouse beta 1- and beta 2-receptor sequence. Receptor binding of[3H]dihydroalprenolol was 123 +/- 13 fmol/mg protein, and a 3:1 ratio of beta 1- to beta 2-receptors was observed with DCT cell membranes. Isoproterenol, a beta-receptor agonist, increased cAMP formation 8.5-fold. Pretreatment with the antagonist propranolol abolished agonist-induced cAMP accumulation. Isoproterenol significantly increased 22Na+ uptake to 345 +/- 23 compared with a basal rate of 256 +/- 12 nmol.min-1.mg protein-1 and was blocked with propranolol and beta 1- and beta 2-selective antagonists. Isoproterenol had no effect on 45Ca2+ entry into DCT cells. In summary, DCT cells express three times more beta 1- than beta 2-receptors and express no detectable beta 3-adrenergic receptors. beta-Receptors couple to adenylyl cyclase, and activation of beta-adrenergic receptors increases Na+ but not Ca2+ entry in DCT cells.

A model of combined feedforward and feedback control of coronary blood flow

1995 ◽  
Vol 268 (2) ◽  
pp. H895-H908 ◽  
Author(s):  
J. K. Miyashiro ◽  
E. O. Feigl
Keyword(s):  
Blood Flow ◽  
Feedback Control ◽  
Coronary Blood Flow ◽  
Feedforward Control ◽  
Receptor Activation ◽  
Balance Model ◽  
Feedback Gain ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Flow Response

Recent evidence shows that norepinephrine affects coronary blood flow not only by alpha-receptor-mediated vasoconstriction and by feedback metabolic vasodilation that occurs as a result of myocardial beta-receptor activation, but also by the direct activation of coronary vascular beta-receptors that increase flow in a feedforward manner. The implications of combined feedforward and feedback control in maintaining the balance between metabolism and flow were investigated in the present mass balance model. Feedback was represented by a closed loop and was based on the hypothesis that the regulated variables are myocardial PO2 and PCO2 and that divergence of these variables from their operating point values functions as the metabolic error signals that manipulate coronary vascular smooth muscle and flow to match metabolism. alpha-Receptor-mediated vasoconstriction and beta-receptor-mediated vasodilation are represented by feedforward open loops that are activated simultaneously with increases in metabolism. The postulated control schemes of 1) metabolic feedback control alone, 2) feedback plus alpha- and beta-adrenergic feedforward control, and 3) feedback plus beta-adrenergic feedforward control were able to simulate the steady-state increase in coronary flow and the decrease in coronary venous PO2 that occurs during comparable experimental conditions. The simulations demonstrate that 1) the speed and accuracy of the flow response improve as beta-adrenergic feedforward control is added and alpha-adrenergic feedforward control is removed from the control scheme, 2) high feedback gain also improves the accuracy of the flow response, but the penalty is instability, and 3) a lag in alpha-adrenergic feedforward control improves the stability of the coronary response.

Hormonal regulation of calcium current in freshly isolated airway smooth muscle cells

1992 ◽  
Vol 262 (3) ◽  
pp. L351-L359 ◽  
Author(s):  
A. Welling ◽  
J. Felbel ◽  
K. Peper ◽  
F. Hofmann
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adrenergic Receptor ◽  
Calcium Current ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Dependent Manner ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Stimulation Of

Single freshly isolated smooth muscle cells of adult bovine trachea were voltage clamped, and the calcium inward current was separated from K+ currents by blocking the large outward currents with intra- and extracellular Cs+ and extracellular tetraethylammonium chloride. Isoproterenol stimulated peak calcium current (ICa) in a dose-dependent manner through the beta-adrenergic receptor. The isoproterenol effect was not mediated or caused by the stimulation of a K+ or Na+ current, a decrease in the intracellular concentrations of Ca2+ or H+, the stimulation of the Na(+)-H+ or the Na(+)-Ca2+ exchanger. Neither basal nor isoproterenol-stimulated ICa was affected by internal dialysis of the cell with adenosine 3',5'-cyclic monophosphate (cAMP), cAMP analogues, or the catalytic subunit of cAMP-kinase. Internal dialysis of the cells with guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) blocked the stimulation of isoproterenol whereas dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) induced an isoproterenol-like maximal increase of ICa. These results show that the beta-adrenergic receptor stimulates the L-type calcium current of isolated tracheal smooth muscle cells independent of cAMP and cAMP-kinase through a GTP/GDP regulated protein.

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