CAN ANYONE HELP?????3 RECEPTOR SITES

QUICK QUESTION ... THERE ARE THREEE RECEPTOR SITES THAT I CANT SEEM TO FIGURE OUT ... B1 B2 B3 RECEPTOR SITES .. THEY SAY CLEN HITS YOUR B3 SITE .. WHEN IM ON CLEN OR T3 I GET NO RESULTS ACCEPT FOR MUSCLE CRAMPING AND NO SLEEP. WHEN IM ON A ECA I GET GREAT RESULTS ... THEY SAY ECA HITS ALL 3 RECEPTOR SITES

IS THIS TRUE ????????????????????

Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans.

Liu YL, Toubro S, Astrup A, Stock MJ.

Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Frederiksberg C, Denmark.

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). DESIGN: 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. SUBJECTS: Nine healthy, young male volunteers at rest after an overnight fast. MEASUREMENTS: 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. CONCLUSION: 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.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 8574280 [PubMed - indexed for MEDLINE]

b -Adrenoceptor Subtypes

The b -adrenoceptors were initially divided into b1 and b2-adrenoceptors defined in terms of agonist potencies, b1-adrenoceptors demonstrated equal affinity for adrenaline and nor- adrenaline while b2-adrenoceptors displayed a higher selectivity for nor-adrenaline than for adrenaline. The discovery of these receptor subtypes led to the development of selective agonists and antagonists for each subtype.

The story does not end there, further experimentation using b-antagonists exposed another receptor subtype which appeared to be insensitive to typical b-adrenoceptor antagonists this was classified as b3-adrenoceptor. More recent pharmacological evidence is now emerging in support of a further receptor subtype b4-adrenoceptor, although as yet there are no selective compounds for this particular subtype.

b-Adrenoceptor Location and Function

b1-receptors are largely postsynaptic and are located mainly in the heart but are also found in platelets, the salivary glands and the non-sphincter part of the gastrointestinal tract (GIT). They can however be found presynaptically. Activation causes an increase in the rate and contractile force of the heart, relaxation of the non-sphincter part of the GIT, aggregation of platelets and amylase secretion from the salivary glands. Presynaptically, their activation causes an increase in noradrenaline release.

b2-receptors are also mainly postsynaptic and are located on a number of tissues including blood vessels, bronchi, GIT, skeletal muscle, liver and mast cell. Activation results in vasodilatation, bronchodilation, relaxation of the GIT, glycogenolysis in the liver, tremor in skeletal muscle and inhibition of histamine release from mast cells.

b3-receptors are expressed predominately in adipose tissue activation is proposed to be involved with noradrenaline induced changes in energy metabolism via lipolysis and thermogenesis.

b4-receptors are localised in cardiac tissue with activation causing an increase in heart rate and force.

Transduction Mechanisms

For all b-adrenoceptors transduction is via G-proteins coupled to the intracellular second messenger adenylate cyclase. All b-receptors are positively coupled to adenylate cyclase via activation of Gs G-protein, however activation of the b2 and b3-adrenoceptors results in stimulation or stimulation and inhibition of adenylate cyclase. Activation of the b1 and b4 receptor results in an increase in the formation of cAMP and the subsequent stimulation of cAMP-dependent protein kinase.

Clinical Uses

Adrenergic drugs are used in the treatment of a wide range of medical conditions. Including the use of b2-receptor selective agonists in the treatment of asthma and other related bronchospastic conditions examples of these drugs include salbutamol and salmeterol. Beta-blocker drugs are commonly used in the treatment of angina pectoris, cardiac arrhythmia and for the long-term treatment of patients who survive myocardial infarction. b-receptor antagonists have also been used as anti-hypertensive for a number of years. Beta -blockers have also proven useful in the treatment of conditions such as migraine, anxiety disorders, hyperthyroidism, alcohol withdrawal and when applied topically are useful in the treatment of glaucoma and ocular hypertension.

thank you ... see what im saying this board is awesome and the mods are extensive and not brief ... respect to the fullest


thanks guys and thanks to superman1975 who has helped me all along

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great info.........