scholarly journals Investigation on .BETA.-adrenoceptor, cyclic nucleotides, adenylate cyclase activity in bronchial asthma.

1986 ◽  
Vol 37 (4) ◽  
pp. 331-346
Author(s):  
Kimiyo Yamasaki
1991 ◽  
Vol 278 (2) ◽  
pp. 587-593 ◽  
Author(s):  
G D Dimitriadis ◽  
S J Richards ◽  
M Parry-Billings ◽  
B Leighton ◽  
E A Newsholme ◽  
...  

1. The actions of the beta-adrenoceptor agonist isoprenaline on glucose and glycogen metabolism, in the presence of various concentrations of insulin, were investigated in isolated soleus muscle preparations taken from eu-, hyper- and hypothyroid rats. 2. Hyperthyroidism, induced by 3,3′,5-tri-iodo-D-thyronine (T3) administration for 5 days, increased the rate of lactate formation and suppressed the rate of glycogen synthesis in soleus muscle in response to isoprenaline, even in the presence of physiological or supraphysiological insulin concentrations. 3. Hypothyroidism, induced by administration of 6-n-propyl-2-thiouracil for 4 weeks, decreased the rate of isoprenaline-stimulated lactate formation at all insulin concentrations, but significantly decreased the responsiveness of lactate formation only at low insulin concentrations. In the presence of 100 or 10,000 mu-units of insulin/ml, the ability of isoprenaline to suppress the rate of glycogen synthesis was markedly impaired (inhibition at 100 mu-units of insulin/ml and 1 micro-M-isoprenaline: eu- 72.6 +/- 2.9%; hypo-41.0 +/- 2.1%; P less than 0.001). 4. Hyperthyroidism had no effect on the number or affinity of beta-adrenoceptors, defined by 125I-pindolol binding, or beta-adrenoceptor- or forskolin-stimulated adenylate cyclase activity in membrane preparations of gastrocnemius muscle, whereas hypothyroidism increased the beta-adrenoceptor density and decreased the beta-adrenoceptor-stimulated adenylate cyclase activity, without affecting the receptor affinity or forskolin-stimulated adenylate cyclase activity. 5. It is concluded that there is a complex interplay between insulin, catecholamines and thyroid hormones to regulate skeletal-muscle glucose metabolism. The changes observed in muscles in hypothyroidism may be explained, at least in part, by changes in beta-adrenoceptor-G-protein-adenylate cyclase coupling affecting the generation of cyclic AMP and the regulation of some of the key enzymes of glycogen metabolism; in contrast, the changes observed in muscles in hyperthyroidism do not appear to result from alterations at the level of the receptor-mediated second-messenger generation.


1997 ◽  
Vol 87 (Supplement) ◽  
pp. 85A
Author(s):  
M. Guennicker ◽  
M. Brinkmann ◽  
U. Freund ◽  
M. Schieffer ◽  
O-E. Brodde ◽  
...  

1999 ◽  
Vol 202 (17) ◽  
pp. 2339-2348 ◽  
Author(s):  
J.A. Riegel ◽  
R.W. Farndale ◽  
S.H. Maddrell

Para-aminohippuric acid (PAH, 0.2 and 1 mmol l(−)(1)) had no effect on the basal fluid secretion rate (FSR) of isolated Malpighian tubules of Drosophila melanogaster Meig. and did not affect stimulation of the FSR induced by adenosine 3′,5′-monophosphate (cAMP). Phenol Red (phenolsulphonphthalein, PSP; 0.5 and 1 mmol l(−)(1)) slowed the FSR and abolished stimulation of the FSR by cAMP. Diodrast (1 mmol l(−)(1)) slightly, but significantly, reduced the FSR and greatly reduced the stimulation of the FSR normally provoked by cAMP and by the 3′,5′-monophosphates of guanosine (cGMP), inosine (cIMP) and uridine (cUMP). However, stimulation of the FSR by the 3′, 5′-monophosphate of cytidine (cCMP) was little affected by diodrast. Probenecid (0.2 or 1 mmol l(−)(1)) consistently stimulated the FSR, on average by approximately 25 %, but did not markedly inhibit the subsequent stimulation of the FSR by cAMP, cGMP or cIMP. However, the FSR of tubules stimulated by cGMP was temporarily lowered by probenecid. Quinacrine (0.1 mmol l(−)(1)) slowed basal FSR by an average of approximately 30 %, but subsequent stimulation of the FSR by cAMP was not noticeably affected. Both 0.1 mmol l(−)(1) cAMP and 1 mmol l(−)(1) probenecid stimulated adenylate cyclase activity in extracts of Malpighian tubules, but cIMP, cGMP, cUMP and diodrast were without effect in this regard. Uptake of radioactivity from a solution containing 500 nmol l(−)(1) [(3)H]cAMP and 9.5 μmol l(−)(1) cAMP was reduced by more than 90 % by 1 mmol l(−)(1) PSP, by approximately 40 % by 0.2 mmol l(−)(1) probenecid, by 36 % by 1 mmol l(−)(1) diodrast and by 30 % by 1 mmol l(−)(1) PAH. Neither 0.01 mmol l(−)(1) ouabain nor 0.1 mmol l(−)(1) quinacrine affected the uptake of [(3)H]cAMP by the Malpighian tubules. Fluid secreted by isolated Malpighian tubules of Drosophila melanogaster contains a factor that stimulated the FSR on average by approximately 50 %. The presence in the secreted fluid of cGMP at a concentration of 8.3 μmol l(−)(1) did not explain the stimulatory effect on FSR. These results support the existence of a carrier-mediated uptake of cyclic nucleotides into the Malpighian tubules of Drosophila melanogaster, possibly involving a multispecific transporter.


Author(s):  
L.S. Cutler

Many studies previously have shown that the B-adrenergic agonist isoproterenol and the a-adrenergic agonist norepinephrine will stimulate secretion by the adult rat submandibular (SMG) and parotid glands. Recent data from several laboratories indicates that adrenergic agonists bind to specific receptors on the secretory cell surface and stimulate membrane associated adenylate cyclase activity which generates cyclic AMP. The production of cyclic AMP apparently initiates a cascade of events which culminates in exocytosis. During recent studies in our laboratory it was observed that the adenylate cyclase activity in plasma membrane fractions derived from the prenatal and early neonatal rat submandibular gland was retractile to stimulation by isoproterenol but was stimulated by norepinephrine. In addition, in vitro secretion studies indicated that these prenatal and neonatal glands would not secrete peroxidase in response to isoproterenol but would secrete in response to norepinephrine. In contrast to these in vitro observations, it has been shown that the injection of isoproterenol into the living newborn rat results in secretion of peroxidase by the SMG (1).


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