Desensitization effect of in vivo treatment with metaproterenol on β1, β2 and β3-adrenergic responsiveness in rat adipocytes

Portillo, Marı́a P.; Barrio, A. S. Del; García-Calonge, María A.; Martínéz, J. Alfredo

doi:10.1016/0024-3205(95)02305-4

Cited by 12 publications

(3 citation statements)

References 32 publications

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“…This, in line with the slow HR reduction during the second landiolol infusion phase, can thus be Fig. 3 Regression analyses of heart rate versus duration of landiolol infusion (a) and heart rate versus concentrations of landiolol in venous blood (b) explained as consequence of a dobutamine-induced downregulation of the β 1 -receptor function, a desensitization phenomenon already described experimentally and clinically in previous investigations [48][49][50][51].…”

Section: Pharmacodynamicssupporting

confidence: 79%

Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults

Krumpl¹,

Ulč²,

Trebs

et al. 2020

BMC Pharmacol Toxicol

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Background To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry. Methods We conducted a single-center, prospective randomized study in 16 healthy subjects each receiving an infusion of dobutamine sufficient to increase heart rate by 30 bpm followed by a 60 min infusion of 10 μg/kg/min landiolol. Results Dobutamine-induced increases in heart rate were stable for at least 20 min before a 60 min landiolol- infusion was started. The dobutamine effects were rapidly antagonized by landiolol within 16 min. A further slight decrease in heart rate during 20–60 min of the landiolol infusion occurred as well. Upon termination of landiolol infusion, heart rate and blood pressure recovered rapidly in response to the persisting dobutamine infusion but did not return to the maximum values before landiolol infusion. The pharmacokinetic parameters of landiolol in presence of dobutamine showed a short half-life (3.5 min) and a low distribution volume (0.3 l/kg). No serious adverse events were observed. Conclusion Landiolol can antagonize the dobutamine-induced increases in heart rate and blood pressure in a fast way. A rapid bradycardic effect until steady-state plasma levels is followed by a slow heart rate reduction. The latter can be attributed to an early desensitization to dobutamine. Consequently, after termination of landiolol, the heart rate did not achieve maximum pre-landiolol values. The pharmacokinetics of landiolol during dobutamine infusion are similar when compared to short- and long-term data in Caucasian subjects. Landiolol in the given dose can thus serve as an antagonist of dobutamine-induced cardiac effects. Trial registration Registration number 2010–023311-34 at the EU Clinical Trials Register, registration date 2010-12-21.

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Section: Pharmacodynamicssupporting

confidence: 79%

Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults

Krumpl¹,

Ulč²,

Trebs

et al. 2020

BMC Pharmacol Toxicol

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“…Recent studies have demonstrated that desensitization of the ␤-adrenergic response in rat adipocytes involves various receptor subtypes and cAMP phosphodiesterase (7). In vivo desensitization of the ␤-adrenergic response was shown in white adipocytes of various species (12,22), and a differential regulation of ␤ 1 -and ␤ 2 -AR has been described (9,32). In humans, during prolonged local epinephrine infusion, concentrations of interstitial glycerol tend to fall after a transient increase (2).…”

mentioning

confidence: 99%

A single bout of exercise induces β-adrenergic desensitization in human adipose tissue

Marion-Latard

Glisezinski

Crampes

et al. 2001

American Journal of Physiology-Regulatory, Integrative and Comp

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This study was designed to assess whether physiological activation of the sympathetic nervous system induced by exercise changes adipose tissue responsiveness to catecholamines in humans. Lipid mobilization in abdominal subcutaneous adipose tissue was studied with the use of a microdialysis method in 11 nontrained men (age: 22. 3 +/- 1.5 yr; body mass index: 23.0 +/- 1.6). Adipose tissue adrenergic sensitivity was explored with norepinephrine, dobutamine (beta(1)-agonist), or terbutaline (beta(2)-agonist) perfused during 30 min through probes before and after 60-min exercise (50% of the maximal aerobic power). The increase in extracellular glycerol concentration during infusion was significantly lower after the exercise when compared with the increase observed before the exercise (P < 0.05, P < 0.02, and P < 0.01, respectively, for norepinephrine, dobutamine, and terbutaline). In a control experiment realized without exercise, no difference in norepinephrine-induced glycerol increase between the two infusions was observed. To assess the involvement of catecholamines in the blunted beta-adrenergic-induced lipolytic response after exercise, adipose tissue adrenergic sensitivity was explored with two 60-min infusions of norepinephrine or epinephrine separated by a 60-min interval. With both catecholamines, the increase in glycerol was significantly lower during the second infusion (P < 0.05). The findings suggest that aerobic exercise, which increased adrenergic activity, induces a desensitization in beta(1)- and beta(2)-adrenergic lipolytic pathways in human subcutaneous adipose tissue.

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“…Changes in sensitivity to leptin's effects could also occur in white adipose tissue. Chronic stimulation of adrenergic receptors is known to result in development of resistance (27), but this effect can vary among adrenergic receptor subtypes (28, 29) and, therefore, could vary among adipose depots, depending on the types and relative amounts of adrenergic receptors present. Although these ideas may be speculative at this point, they do suggest directions for further research into the mechanisms involved in leptin‐induced adipose tissue apoptosis and the development of selective resistance to leptin, both of which could have important implications for the treatment of obesity.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of ob/ob Mice to Leptin‐Induced Adipose Tissue Apoptosis

et al. 2005

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Research Methods and Procedures:Fifteen-week-old female ob/ob and Ob/? mice received 0 (saline), 2.5, or 10 g/d leptin for 14 days through subcutaneous (sc) osmotic minipumps. Food intake (FI), body temperature, physical activity, and body weight were measured daily. Body composition and weights and adipose tissue apoptosis (percentage DNA fragmentation) of inguinal, parametrial, and retroperitoneal fat pads were determined at the end of the study. Results: FI decreases were more pronounced in ob/ob. Leptin (10 g/d) decreased total FI 71% in ob/ob and 34% in Ob/? (p Ͻ 0.05). Body weight was decreased by both doses of leptin in ob/ob (p Ͻ 0.01) but was unchanged in Ob/?. Leptin increased body temperature in ob/ob but not in Ob/?. Physical activity was increased 400% by 10 g/d leptin in ob/ob (p Ͻ 0.01) but decreased 13% in Ob/? (p Ͻ 0.01). Body fat content of ob/ob was reduced by both leptin doses, whereas only 10 g/d leptin decreased body fat in Ob/?. Fat pad weights were decreased similarly by leptin in both genotypes. However, apoptosis was increased by leptin in all three fat pads in ob/ob, whereas Ob/? showed significant increases only in retroperitoneal. Discussion: ob/ob mice had greater overall sensitivity to leptin. Although ob/ob mice appeared to be more sensitive than Ob/? mice to leptin-induced adipose tissue apoptosis, there were differences among adipose depots in responsiveness to leptin-induced apoptosis.

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Desensitization effect of in vivo treatment with metaproterenol on β1, β2 and β3-adrenergic responsiveness in rat adipocytes

Cited by 12 publications

References 32 publications

Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults

Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults

A single bout of exercise induces β-adrenergic desensitization in human adipose tissue

Sensitivity of ob/ob Mice to Leptin‐Induced Adipose Tissue Apoptosis

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