Prolonged administration in vivo of alpha and beta adrenergic agonists decreases insulin binding to rat myocardial membranes in vitro by different mechanisms

Life Sciences ◽  
1991 ◽  
Vol 48 (23) ◽  
pp. 2249-2258 ◽  
Author(s):  
G. Desoye ◽  
U. Ertl-Stockinger ◽  
S. Porta
Keyword(s):  
Insulin Binding ◽  
Adrenergic Agonists ◽  
Prolonged Administration ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
Myocardial Membranes

Sympathetic nervous system and renin release from submaxillary glands in vitro

1976 ◽  
Vol 231 (2) ◽  
pp. 551-554 ◽  
Author(s):  
AM Michelakis ◽  
JW Menzie ◽  
H Yoshida
Keyword(s):  
Direct Action ◽  
Submaxillary Gland ◽  
Renin Release ◽  
Adrenergic Agonists ◽  
Beta Adrenergic ◽  
Submaxillary Glands ◽  
Beta Adrenergic Agonists ◽  
Camp Levels

We previously reported that alpha- but not beta-adrenergic agonists stimulate renin release from mouse submaxillary glands in vivo. The present studies were undertaken to determine if these in vivo effects were due to a direct action on the submaxillary glands and to find out if cyclic AMP (cAMP) might be involved in submaxillary renin release. Pooled mouse submaxillary gland slices were incubated in Krebs-Ringer bicarbonate medium following a preincubation period, and renin release was measured by a radioimmunoassay for the direct measurement of submaxillary gland renin. Tissue cAMP levels were also measured. Addition of the alpha-adrenergic agonists, phenylephrine or norepinephrine, significantly increased renin release (P less than 0.01 vs. control) while decreasing tissue cAMP levels (P less than 0.01 vs. control). In contrast, addition of the beta-adrenergic agonist isoproterenol markedly increased cAMP levels (P less than 0.01 vs. control) and decreased renin release (P less than 0.05 vs. control). Pretreatment of the slices with the alpha-blocker phenoxy genzamine inhibited the effect of phenylephrine. These results indicate that alpha-adrenergic agonists cause renin release from submaxillary glands which is accompanied by a fall in tissue cAMP levels. This is in contrast to renin release from the kidney which is stimulated by beta-adrenergic agonists.

Regulation of Trypanosoma cruzi infectivity by alpha- and beta-adrenergic agonists: desensitization produced by prolonged treatments or increasing agonist concentrations

Parasitology ◽  
1990 ◽  
Vol 100 (3) ◽  
pp. 429-434 ◽  
Author(s):  
A. Ayala ◽  
F. Kierszenbaum
Keyword(s):  
Trypanosoma Cruzi ◽  
Prolonged Exposure ◽  
Inhibitory Effect ◽  
Tissue Level ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
Alpha Adrenergic Agonist

SUMMARYWe previously reported that blood forms of Trypanosoma cruzi express alpha- and beta-adrenergic receptors and that binding of specific agonists to these receptors modifies the infective capacity of the parasite in vitro. The present study has revealed that the inhibitory effect of the beta-adrenergic agonist L-isoproterenol and the stimulatory effect of the alpha-adrenergic agonist L-phenylephrine are not produced when the parasite is subjected to prolonged exposure to otherwise effective doses of these agonists or when supraoptimal doses of these agonists are used. We refer to these phenomena as ‘desensitization’ because of their analogy with vertebrate cells becoming desensitized by prolonged exposure to, or relatively high concentrations of, adrenergic agonists. At a constant agonist concentration, T. cruzi desensitization was time-dependent and, when the time of parasite treatment with the agonists was not changed, the higher concentrations of the agonist tested were the most effective in producing desensitization. The reduced infectivity resulting from treatment with optimal doses of L-isoproterenol was accompanied by elevated levels of cyclic adenosine mono- phosphate (cAMP) which were not detectable when L-isoproterenol concentrations producing desensitization were used. This finding implicated cAMP as a likely second signal in the inhibitory mechanisms of this agonist. No significant change in cAMP was detectable in parasites treated with L-phenylephrine, leaving open the question about how optimal doses of this alpha-adrenergic agonist enhance T. cruzi infectivity. Parasite responsiveness to alpha- and beta-adrenergic agonists as well as the desensitization effects define a system which regulates infectivity and could be modified at the host tissue level by naturally occurring agonists.

scholarly journals The sites of phosphorylation by protein kinase C and an intact SH2 domain are required for the enhanced response to beta-adrenergic agonists in cells overexpressing c-src.

1993 ◽  
Vol 13 (4) ◽  
pp. 2391-2400 ◽  
Author(s):  
J S Moyers ◽  
A H Bouton ◽  
S J Parsons
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Beta Agonist ◽  
Adrenergic Agonists ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
Kinase C ◽  
Gs Alpha ◽  
In Cells

Previously we demonstrated that C3H10T1/2 murine fibroblasts overexpressing avian c-src exhibit elevated levels of cyclic AMP (cAMP) in response to beta-adrenergic agonists compared with that in control cells and that this enhanced response requires c-src kinase activity (W. A. Bushman, L. K. Wilson, D. K. Luttrell, J. S. Moyers, and S. J. Parsons, Proc. Natl. Acad. Sci. USA 87:7462-7466, 1990). However, it is not yet known which components of the beta-adrenergic receptor pathway, if any, interact with pp60c-src. It has recently been shown that immune complexes of pp60c-src phosphorylate recombinant G alpha proteins in vitro to stoichiometric levels, resulting in alterations of GTP binding and GTPase activity (W. P. Hausdorff, J. A. Pitcher, D. K. Luttrell, M. E. Linder, H. Kurose, S. J. Parsons, M. G. Caron, and R. J. Lefkowitz, Proc. Natl. Acad. Sci. USA 89:5720-5724, 1992), raising the possibility that the Gs alpha protein may be an in vivo target for the interaction with pp60c-src. To further characterize the involvement of pp60c-src in the beta-adrenergic signalling pathway, we have overexpressed, in 10T1/2 cells, pp60c-src containing mutations in several domains which are believed to be important for signalling processes. In this study we show that the sites of phosphorylation by protein kinase C (PKC) (Ser-12 and Ser-48) as well as the SH2 region of pp60c-src are required for the enhanced response of c-src overexpressors to beta-agonist stimulation. Mutation at the site of myristylation (Gly-2) results in a decrease in the enhanced response, while mutation at the site of phosphorylation by cAMP-dependent protein kinase (Ser-17) has no effect. Two-dimensional phosphotryptic analyses indicate that phosphorylation on Ser-12 and Ser-48 in unstimulated cells is associated with the ability of overexpressed pp60c-src to potentiate beta-adrenergic signalling. Cells overexpressing wild-type c-src also exhibit enhanced cAMP accumulation upon treatment with cholera toxin, an effect that is abated in cells overexpressing pp60c-src defective in the kinase or SH2 domains or altered at the sites of phosphorylation by PKC. These studies provide the first evidence for the physiological significance of the pp60c-src sites of PKC phosphorylation. In addition, they show that the SH2, Ser-12/48, and myristylation regions may be important for efficient interaction of pp60c-src with components of the beta-adrenergic pathway. Our data also support the possibility that the Gs alpha protein may be an in vivo target for alteration by pp60c-src.

scholarly journals The rate of substrate cycling between fructose 6-phosphate and fructose 1,6-bisphosphate in skeletal muscle

1984 ◽  
Vol 221 (1) ◽  
pp. 153-161 ◽  
Author(s):  
R A J Challiss ◽  
J R S Arch ◽  
E A Newsholme
Keyword(s):  
Exchange Chromatography ◽  
Adrenergic Agonists ◽  
Beta Adrenergic ◽  
Cycling Rate ◽  
Physiological Importance ◽  
Beta Adrenergic Agonists ◽  
Fructose 1,6 Bisphosphatase ◽  
Adrenergic Antagonists ◽  
Fructose 1,6 Bisphosphate

Substrate cycling of fructose 6-phosphate through reactions catalysed by 6-phosphofructokinase and fructose-1,6-bisphosphatase was measured in skeletal muscles of the rat in vitro. The rate of this cycle was calculated from the steady-state values of the 3H/14C ratio in hexose monophosphates and fructose 1,6-bisphosphate after the metabolism of either [5-3H,6-14C]glucose or [3-3H,2-14C] glucose. Two techniques for the separation of hexose phosphates were studied; t.l.c. chromatography on poly(ethyleneimine)-cellulose sheets or ion-exchange chromatography coupled with enzymic conversion. These two methods gave almost identical results, suggesting that either technique could be used for determination of rates of fructose 6-phosphate/fructose 1,6-bisphosphate cycling. It was found that more than 50% of the 3H was retained in the fructose 1,6-bisphosphate; it is therefore probable that previous measurement of cycling rates, which have assumed complete loss of 3H, have underestimated the rate of this cycle. The effects of insulin, adrenaline and adrenergic agonists and antagonists on rates of fructose 6-phosphate/fructose 1,6-bisphosphate cycling were investigated. In the presence of insulin, adrenaline (1 microM) increased the cycling rate by about 10-fold in epitrochlearis muscle in vitro; the maximum rate under these conditions was about 2.5 mumol/h per g of tissue. The concentration of adrenaline that increased the cycling rate by 50% was about 50 nM. This effect of adrenaline appears to be mediated by the beta-adrenergic receptor, since the rate was increased by beta-adrenergic agonists and blocked by beta-adrenergic antagonists. From the knowledge of the precise rate of this cycle, the possible physiological importance of cycling is discussed.

The sites of phosphorylation by protein kinase C and an intact SH2 domain are required for the enhanced response to beta-adrenergic agonists in cells overexpressing c-src

1993 ◽  
Vol 13 (4) ◽  
pp. 2391-2400
Author(s):  
J S Moyers ◽  
A H Bouton ◽  
S J Parsons
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Beta Agonist ◽  
Adrenergic Agonists ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
Kinase C ◽  
Gs Alpha ◽  
In Cells

Previously we demonstrated that C3H10T1/2 murine fibroblasts overexpressing avian c-src exhibit elevated levels of cyclic AMP (cAMP) in response to beta-adrenergic agonists compared with that in control cells and that this enhanced response requires c-src kinase activity (W. A. Bushman, L. K. Wilson, D. K. Luttrell, J. S. Moyers, and S. J. Parsons, Proc. Natl. Acad. Sci. USA 87:7462-7466, 1990). However, it is not yet known which components of the beta-adrenergic receptor pathway, if any, interact with pp60c-src. It has recently been shown that immune complexes of pp60c-src phosphorylate recombinant G alpha proteins in vitro to stoichiometric levels, resulting in alterations of GTP binding and GTPase activity (W. P. Hausdorff, J. A. Pitcher, D. K. Luttrell, M. E. Linder, H. Kurose, S. J. Parsons, M. G. Caron, and R. J. Lefkowitz, Proc. Natl. Acad. Sci. USA 89:5720-5724, 1992), raising the possibility that the Gs alpha protein may be an in vivo target for the interaction with pp60c-src. To further characterize the involvement of pp60c-src in the beta-adrenergic signalling pathway, we have overexpressed, in 10T1/2 cells, pp60c-src containing mutations in several domains which are believed to be important for signalling processes. In this study we show that the sites of phosphorylation by protein kinase C (PKC) (Ser-12 and Ser-48) as well as the SH2 region of pp60c-src are required for the enhanced response of c-src overexpressors to beta-agonist stimulation. Mutation at the site of myristylation (Gly-2) results in a decrease in the enhanced response, while mutation at the site of phosphorylation by cAMP-dependent protein kinase (Ser-17) has no effect. Two-dimensional phosphotryptic analyses indicate that phosphorylation on Ser-12 and Ser-48 in unstimulated cells is associated with the ability of overexpressed pp60c-src to potentiate beta-adrenergic signalling. Cells overexpressing wild-type c-src also exhibit enhanced cAMP accumulation upon treatment with cholera toxin, an effect that is abated in cells overexpressing pp60c-src defective in the kinase or SH2 domains or altered at the sites of phosphorylation by PKC. These studies provide the first evidence for the physiological significance of the pp60c-src sites of PKC phosphorylation. In addition, they show that the SH2, Ser-12/48, and myristylation regions may be important for efficient interaction of pp60c-src with components of the beta-adrenergic pathway. Our data also support the possibility that the Gs alpha protein may be an in vivo target for alteration by pp60c-src.

Exercise training and responsiveness of isolated coronary arteries

1991 ◽  
Vol 71 (6) ◽  
pp. 2346-2351 ◽  
Author(s):  
P. J. Rogers ◽  
T. D. Miller ◽  
B. A. Bauer ◽  
J. M. Brum ◽  
A. A. Bove ◽  
...  
Keyword(s):  
Exercise Training ◽  
Coronary Arteries ◽  
Vasoactive Intestinal Polypeptide ◽  
Adrenergic Agonists ◽  
Response Curves ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
The Right ◽  
Intestinal Polypeptide

Exercise is associated with release of catecholamines and vasoactive intestinal polypeptides. Recurrent exposure to catecholamines modifies the sensitivity of adrenoceptors. To test the hypothesis that exercise training may affect the sensitivity of the epicardial coronary arteries, we performed studies on isolated coronary arteries from male dogs capable of running on a treadmill. The animals were separated randomly into two groups: sedentary and exercise training. After 11 wk, rings of left circumflex and left anterior descending coronary arteries were studied in vitro. Contractions to alpha 1-adrenergic agonists (norepinephrine and phenylephrine) were not affected by exercise training. During contractions with prostaglandin F2 alpha, endothelium-dependent relaxations to alpha 2-adrenergic agonists (norepinephrine and UK 14304) were not reduced significantly by exercise training. The concentration-relaxation curves to beta-adrenergic agonists (norepinephrine, isoproterenol, and epinephrine) were shifted to the right after training. The concentration-response curves to vasoactive intestinal polypeptide, but not that to substance P, were shifted to the right in rings with endothelium from exercise-trained animals. These findings demonstrate a decrease in responsiveness of canine vascular smooth muscle to beta-adrenergic agonists and to vasoactive intestinal polypeptide after exercise training.

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