Digoxin reduces beta-adrenergic contractile response in rabbit hearts. Ca(2+)-dependent inhibition of adenylyl cyclase activity via Na+/Ca2+ exchange.

Inflammation, increased cytokine production, and decreased responsiveness of airway smooth muscle (ASM) to beta-adrenergic agonists are characteristics of asthma. We questioned whether the cytokine tumor necrosis factor-alpha (TNF-alpha) directly impaired beta-adrenergic signal transduction in cultured canine ASM cells. Confluent ASM cells exposed to TNF-alpha (0.1-10 ng/ml) for 72 h showed lower maximal levels of adenylyl cyclase activity in response to isoproterenol (10 ng/ml; 14 +/- 4.3 vs. 7.5 +/- 1.3 pmol adenosine 3',5'-cyclic monophosphate x well(-1) x 20 min(-1), control vs. treated, respectively), despite no changes in beta-adrenergic receptor numbers (maximum number of binding sites = 4.8 +/- 0.72 vs. 4.5 +/- 0.81 fmol/mg protein, control vs. treated, respectively). Adenylyl cyclase activities in response to prostaglandin E1, NaF, or forskolin were not different in treated and untreated cells. These results demonstrate that a cytokine known to be increased during exacerbation of asthmatic symptoms directly impairs beta-adrenergic function in ASM cells and suggests a mechanism by which inflammation impairs beta-adrenergic receptor signal transduction in asthma.

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Pepsinogen release from isolated gastric glands

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1982.243.3.g218 ◽

1982 ◽

Vol 243 (3) ◽

pp. G218-G225 ◽

Cited By ~ 2

Author(s):

H. R. Koelz ◽

S. J. Hersey ◽

G. Sachs ◽

C. S. Chew

Keyword(s):

Adenylyl Cyclase ◽

Cyclase Activity ◽

Dependent Manner ◽

Adrenergic Stimulation ◽

Adenylyl Cyclase Activity ◽

Gastric Glands ◽

Beta Adrenergic ◽

Camp Content ◽

Isolated Gastric Glands ◽

Dose Dependent

The in vitro release of pepsinogen was studied using a preparation of isolated gastric glands from rabbits. The pepsinogen content of the glands was estimated to be about 700 U/mg dry wt. Spontaneous release of pepsinogen was found to be less than 1% of the total per hour and relatively constant for at least 2 h. Pepsinogen release was stimulated in a dose-dependent manner by both carbachol and isoproterenol. The cholinergic and beta-adrenergic stimulation was selectively inhibited by atropine and propranolol, respectively. Removal of external calcium inhibited the responses to both isoproterenol (partially) and carbachol (completely). Several agents, including histamine, prostaglandin (E2), and synthetic secretin, were found not to stimulate pepsinogen release. However, a crude secretin preparation (Boots) was found to produce significant stimulation. Dibutyryl cAMP increased pepsinogen release in a dose-dependent manner. Isoproterenol was found to increase the cAMP content of gastric glands and to stimulate adenylyl cyclase activity in homogenates. The beta-adrenergic stimulation of adenylyl cyclase was found to be selective for a population of gastric cells that was relatively depleted of parietal cells and distinct from the histamine-stimulated adenylyl cyclase activity. The results indicate that pepsinogen secretion by the gastric chief cell is regulated, in part, by separate cholinergic and beta-adrenergic mechanisms and that both calcium and cAMP play a role in this regulation.

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Beta-adrenergic receptor in the brain: Comparison of 3H-dihydroalprenolol binding sites and a beta-adrenergic receptor regulating adenylyl cyclase activity in cell free homogenates

Life Sciences ◽

10.1016/0024-3205(78)90470-8 ◽

1978 ◽

Vol 23 (16) ◽

pp. 1703-1713 ◽

Cited By ~ 11

Author(s):

Thomas E. Cote ◽

John W. Kebabian

Keyword(s):

Adenylyl Cyclase ◽

Binding Sites ◽

Adrenergic Receptor ◽

Cyclase Activity ◽

Adenylyl Cyclase Activity ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

The Brain

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Liver beta-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes

AJP Cell Physiology ◽

10.1152/ajpcell.1994.266.6.c1664 ◽

1994 ◽

Vol 266 (6) ◽

pp. C1664-C1672 ◽

Cited By ~ 18

Author(s):

N. Begin-Heick

Keyword(s):

Adenylyl Cyclase ◽

G Proteins ◽

Binding Sites ◽

Adrenergic Receptor ◽

Cyclase Activity ◽

Adenylyl Cyclase Activity ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Obesity And Diabetes ◽

Liver Membranes

The ob and db genes produce similar hormonal anomalies in mice. Although the expression of the syndromes diverges with age, at 8-12 wk both ob/ob and db/db mice are hyperglycemic and hyperinsulinemic and show evidence of hypercorticoidism. Nevertheless, membranes isolated from livers of ob/ob and db/db mice behave differently in terms of adenylyl cyclase activity and beta-adrenergic receptor function. There are three times as many beta 2-adrenergic receptor binding sites and a threefold increase in the response to catecholamines in ob/ob mouse liver membranes than in comparable preparations from normal controls or db/db mice. By contrast, the two main G proteins of liver membranes (Gs alpha and Gi alpha 2) are less abundant in the mutants, ob/ob and db/db, than in their respective lean controls. Adrenalectomy normalizes the exaggerated response to beta-adrenergic agonists and the number of beta-adrenergic binding sites in the ob/ob mouse. This shows that the enhanced beta-adrenergic receptor response is linked to hypercorticoidism. Cellular maturation and differentiation (D. C. Watkins, J. K. Northrup, and C. C. Malbon, J. Biol. Chem. 262: 10651-10657, 1987) and diseases such as obesity and diabetes (cf. N. McFarlane-Anderson, J. Bailly, and N. Begin-Heick, Biochem. J. 282: 15-23, 1992) have been associated with modifications in the complement of G proteins detected in cells. However, the relationship among levels, types, and intracellular localization of G proteins in tissues and their influence on the transduction of the message to an effector system, such as adenylyl cyclase, are not yet well understood.

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Effects of coronary arterial reperfusion on beta-adrenergic receptor-adenylyl cyclase coupling

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.1.h196 ◽

1993 ◽

Vol 264 (1) ◽

pp. H196-H204 ◽

Cited By ~ 4

Author(s):

D. E. Vatner ◽

K. Kiuchi ◽

W. T. Manders ◽

S. F. Vatner

Keyword(s):

Adenylyl Cyclase ◽

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Cyclase Activity ◽

Receptor Density ◽

Beta Adrenergic Receptors ◽

Adenylyl Cyclase Activity ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

High Affinity

The effects of 1 h of coronary arterial occlusion (CAO) followed by 15 min reperfusion (CAR) were examined in nine conscious dogs. Ischemia was verified by decreased regional blood flow (radioactive microspheres) and loss of systolic regional wall motion in the ischemic zone. beta-Adrenergic receptor density assessed by 125I-labeled cyanopindolol binding in a crude membrane fraction tended to decrease but was not significantly different. However, adenylyl cyclase activity and the guanine nucleotide stimulatory protein (Gs) were reduced in ischemic subendocardium compared with nonischemic subendocardium. The fraction of beta-adrenergic receptors binding agonist with high affinity increased in ischemic subendocardial and subepicardial layers. Compared with prior data in experiments with 1 h CAO without CAR, the increase in beta-adrenergic receptor density that occurs with myocardial ischemia is rapidly reversed with CAR of 15 min duration, while the decreased fraction of receptors binding agonist with high affinity was reversed to an increase in high-affinity receptors. The global decreases in adenylyl cyclase and Gs, which have been observed with simple CAO, persist but are observed selectively in the previously ischemic subendocardium after CAR. Thus both CAO and CAR affect beta-adrenergic receptors and adenylyl cyclase differently. During CAR, increased numbers of beta-adrenergic receptors binding agonist with high affinity occur potentially as a compensatory mechanism in the face of persistent reductions in adenylyl cyclase activity and Gs.

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