Inhibitory potency of isoprenaline on guinea-pig and gravid human myometrium following extraneuronal uptake blockade

1995 ◽  
Vol 7 (1) ◽  
pp. 59
Author(s):  
M Kousides ◽  
ME Story ◽  
JN Pennefather ◽  
SP Ziccone ◽  
AW Ross
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Human Myometrium ◽  
Inhibitory Effects ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists ◽  
Myometrial Contractility ◽  
Beta Adrenoceptor Agonists ◽  
Evoked Contractions

The hypothesis that inhibitory effects of isoprenaline on myometrial contractility may be constrained by activation of putative intracellular beta-adrenoceptors negatively-coupled to adenylate cyclase was examined. Field-stimulated preparations of guinea-pig and human myometrium were used to examine the influence of the catecholamine extraneuronal uptake2 inhibitors, corticosterone and beta-oestradiol, on the inhibitory effects of the beta-adrenoceptor agonist, isoprenaline, on uterine contraction. Longitudinal and circular myometrial layers were obtained from guinea-pigs in dioestrus, primed with oestrogen before progesterone, or pregnant (Days 62-65). In the guinea-pig myometrium, corticosterone (30 microM) did not affect responses to isoprenaline. beta-oestradiol (10 microM) induced a small potentiation of the effects of isoprenaline on longitudinal myometrium from dioestrus guinea-pigs. Myometrial preparations were obtained from pregnant women (36-40 weeks gestation) undergoing caesarean section. Isoprenaline inhibited stimulation-evoked contractions in 7 of 10 preparations of the inner myometrial layer and in 5 of 8 preparations of outer myometrial layer. Corticosterone (30 microM) reduced the effects of isoprenaline on the inner layer and did not affect the outer layer. These results do not support the existence of mechanism involving isoprenaline-sensitive intracellular receptors which constrain responses to beta-adrenoceptor agonists.

Interaction of iberiotoxin with beta-adrenoceptor agonists and sodium nitroprusside on guinea pig trachea

1993 ◽  
Vol 74 (4) ◽  
pp. 1879-1884 ◽  
Author(s):  
T. R. Jones ◽  
L. Charette ◽  
M. L. Garcia ◽  
G. J. Kaczorowski
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Sodium Nitroprusside ◽  
Airway Smooth Muscle ◽  
Plasma Membranes ◽  
K Channel ◽  
K Channels ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Agonists ◽  
Beta Adrenoceptor Agonists

Airway smooth muscle plasma membranes contain a variety of functional K+ channels. In particular, there is a predominance of Ca(2+)-activated K+ channels (maxi-K). Inhibition of these K+ channels has been postulated to account for the ability of charybdotoxin (ChTX) to produce contraction of airway smooth muscle and to modify the relaxant effects of beta-adrenoceptor agonists and sodium nitroprusside (SNP). Iberiotoxin (IbTX) is more selective and more potent than ChTX at blocking maxi-K channels. In this study, pharmacological experiments were performed on guinea pig trachea to determine whether IbTX produced effects similar to ChTX. The concentration-response curves to salbutamol were markedly affected by IbTX, with a > 60-fold rightward shift being produced with 20 nM IbTX. The maximal relaxation to salbutamol was reduced to 49.3 +/- 0.9, 22.3 +/- 4.7, and 15.0 +/- 2.7% of control maximum in the presence of 20, 60, and 180 nM IbTX, respectively. Similar to salbutamol, the maximal relaxation to SNP was reduced to 80 +/- 1.6, 19 +/- 1.7, and 12 +/- 2.1% of control maximum in the presence of 20, 60, and 180 nM IbTX, respectively. IbTX (180 nM) failed to produce a significant alteration of relaxation to the ATP-dependent K+ channel agonist BRL-34915. Exposure of tissues to K(+)-rich medium (80 mM) inhibited responses to salbutamol > or = SNP > isoproterenol. These results confirm and extend our earlier observations that maxi-K channels may be involved in regulating tone and relaxation of carbachol-contracted guinea pig tracheal smooth muscle. This mechanism is of particular importance for beta 2-adrenoceptor- and SNP-induced relaxation.

Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion

1985 ◽  
Vol 108 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Bo Ahrén
Keyword(s):  
Thyroid Hormone ◽  
Dose Level ◽  
Hormone Secretion ◽  
High Dose ◽  
Inhibitory Effects ◽  
High Dose Level ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists

Abstract. The effects of various α-adrenoceptor agonists and antagonists on blood radioiodine levels were studied in mice pre-treated with 125I and thyroxine. The non-selective α-adrenoceptor agonist noradrenaline and the selective α1-adrenoceptor agonist phenylephrine both enhanced blood radioiodine levels. Noradrenaline was more potent than phenylephrine. Contrary, the selective α2-adrenoceptor agonist clonidine depressed basal levels of blood radioiodine. The non-selective α-adrenoceptor antagonist phentolamine and the selective α1-adrenoceptor antagonist prazosin both inhibited the noradrenaline-induced elevation of radioiodine levels, whereas the α2-adrenoceptor antagonist yohimbine had no such effect, except at a high dose level. All three α-adrenoceptor agonists, noradrenaline, phenylephrine and clonidine, inhibited the radioiodine response to TSH. In addition, TSH-induced increase in radioiodine levels was inhibited by prazosin, whereas yohimbine had no effect. Phentolamine inhibited the radioiodine response to TSH when given 2 h prior to TSH, whereas when given 15 min prior to TSH the response to TSH was potentiated by Phentolamine. It is concluded, that under in vivo conditions in the mouse, α1-adrenoceptor activation stimulates basal thyroid hormone secretion and inhibits TSH-induced thyroid hormone secretion. Further, α2-adrenoceptor activation inhibits basal thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by α1-adrenoceptor antagonism. Thus, α-adrenoceptors induce both stimulatory and inhibitory effects of thyroid function.

scholarly journals Salbutamol-induced severe lactic acidosis in acute asthma

2020 ◽  
Vol 8 ◽  
pp. 2050313X2096902 ◽  
Author(s):  
Hamza Najout ◽  
Mohamed Moutawakil ◽  
Abdelghafour Elkoundi ◽  
Nawfal Doghmi ◽  
Hicham Bekkali
Keyword(s):  
Lactic Acidosis ◽  
Acute Asthma ◽  
Krebs Cycle ◽  
Bronchial Obstruction ◽  
Compensatory Mechanism ◽  
Severe Lactic Acidosis ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Agonists ◽  
Lactate Formation ◽  
Beta Adrenoceptor Agonists

Selective beta-adrenoceptor agonists are worldwide prescribed to manage bronchial obstruction. However, they expose to a potential risk of hyperlactatemia and lactic acidosis even with normal doses. The mechanism still poorly understood and suggested that salbutamol diverts the metabolism of pyruvate acid from Krebs cycle toward lactate formation. We report the case of a 42-year-old patient, admitted to intensive care unit for acute severe asthma. He presented a transient lactic acidosis over the first 48 h, following an excessive use of salbutamol. The metabolic acidosis caused tachypnea, as a compensatory mechanism, leading to respiratory failure. The diagnosis of salbutamol-induced lactic acidosis must be made by elimination and only accepted after deleting the other causes. The main clinical character is the worsening of dyspnea despite regression of bronchospasm. It is transient and usually normalizes within 24–48 h after stopping or decreasing doses of salbutamol.

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