Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans.
OBJECTIVE
To investigate the contribution of beta 3-adrenoceptor activation to sympathetic stimulation of thermogenesis in humans using a sympathomimetic (ephedrine) in combination with a non-selective beta-adrenoceptor antagonist (nadolol).


METHODS
Three doses (2.5, 5 and 10 mg) of nadolol were used to estimate what fraction of the thermogenic response to ephedrine (30 mg) remained after inhibition of beta 1- and beta 2-adrenoceptor mediated responses.


METHODS
Nine healthy, young male volunteers at rest after an overnight fast.


METHODS
Energy expenditure, respiratory quotient, heart rate, blood pressure and plasma potassium, glucose, lactate, glycerol, NEFA and triglycerides were measured before, and for 3 h after treatment with placebo, ephedrine and ephedrine plus three doses of nadolol.


RESULTS
Ephedrine produced significant increases in energy expenditure (thermogenesis), heart rate, systolic blood pressure and plasma glucose; the other parameters measured did not change significantly. Nadolol caused significant inhibition of all responses, but 43% of the thermogenic response to ephedrine remained after the 2.5 mg dose of nadolol, whereas the same dose completely inhibited the heart rate and plasma glucose responses.


CONCLUSIONS
All three beta-adrenoceptor subtypes (beta 1, beta 2 and beta 3) may be involved in ephedrine-induced thermogenesis, but the resistance to complete inhibition by the non-selective antagonist nadolol indicates that at least 40% of the response is mediated by an atypical receptor, which is presumed to be the beta 3-adrenoceptor.
Liu
Y L
YL
Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Frederiksberg C, Denmark.
Toubro
S
S
Astrup
A
A
Stock
M J
MJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000502:physiology; D004809:Ephedrine / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D009248:Nadolol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D011188:Potassium / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012119:Respiration / Q000502:physiology; D016037:Single-Blind Method; D013566:Sympathomimetics / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D009248:Nadolol; D004809:Ephedrine; D005990:Glycerol; D011188:Potassium; D009638:Norepinephrine