JS-adrenoceptor

Several findings support this model. For instance, an early report suggested that there is a positive correlation between the density of (postsynaptic) jS-adrenoceptors in rat cortex and behavioural resistance to a mild environmental stress (novelty and frustration) but a negative correlation between these parameters when the stress is intensified (Stanford and Salmon 1992). More recently, it has been proposed that the phasic response of neurons in the locus coeruleus (which governs attentiveness ) depends on their tonic activity (which determines arousal). Evidence suggests that the relationship between these two parameters is described by a bell-shaped curve and so an optimal phasic response is manifest only at intermediate levels of tonic activity (Rajkowski et al. 1998). 

A logical conclusion from this work was that depression is caused by hyperresponsive )S-adrenoceptors. At first, this might seem to undermine Schildkraut s suggestion that depression is caused by a deficit in noradrenergic transmission. However, proliferation of receptors is the normal response to a deficit in transmitter release and so the opposite change, dowmegulation of jS-adrenoceptors by antidepressants, would follow an increase in the concentration of synaptic noradrenaline. This would be consistent with both their proposed mechanism of action and the monoamine theory for depression. 

To be ready for the next odor stimulus, jS-adrenoceptor kinase (Bark) 2 inactivates a receptor only a tenth of a second after the first stimulation occurred. This kinase phosphorylates the activated receptor, which allows another protein, B-arrestin, to bind to the receptor and inactivate it. This is a specific example of a group of enzymes that deactivate hormone or neuroreceptors (Dawson et al., 1993). 

Hyperthyroidism is characterized by an enhanced sympathetic activity, especially in the heart. The salutary inhibition of jS-adrenoceptors under these conditions can be achieved by all jS-blocker alike. Some of the clinically used compounds are able to reduce the conversion (de-iodination) of thyroxine (T4) to the active 3,5,3 -Triiodothyronine (T3)... 

The enzyme phosphodiesterase (type III) catalyzes the biode-gradation of cyclic AMP (cAMP). Inhibition of this enzyme will cause accumulation of the nucleotide cAMP and hence induces an increase in cardiac contractile force. This effect does not involve cardiac jS-adrenoceptors and will therefore persist after downregulation of these receptors associated with heart failure. 

Table 1. Characteristics of potential F-labeled jS-adrenoceptor PET radioligands... 

Riddell JG, Shanks RG. Effects of betaxolol, propranolol, and atenolol on isoproterenol-induced jS-adrenoceptor responses. Clin Pharmacol Ther 1985 38 554-559. 

Receptor Cell surface GPCR Muscarinic, dopamine jS-adrenoceptor GABAb... 

Cawthorne, M.A., 1990. Thermogenic drugs. The potential of selective jS-adrenoceptor agonists as anti-obesity drugs. In Oomura, Y. et al, (Eds.), Progress in Obesity Research. John Libbey, pp. 567-574. 

Bourne GR The metabolism of jS-adrenoceptor blocking drugs. Progress in Drug Metab. London, U.K., John Wiley Sons, 1981 6 77-110. 

Knowledge of the chemistry of local anaesthetics also helps in finding possible substitutes, e.g., the replacement of an ester by an amide agent which neither cross-reacts, nor is likely to cause allergy by itself. Many other compounds have local anaesthetic properties, and may be thought of as potential alternatives, e.g., certain phenothiazine antihistamines and propranolol (the jS-adrenoceptor blocker). 

This salicylamide compound has been shown in animals and man to have both a-and jS-adrenoceptor blocking properties. When it was studied in 20 patients over a period of 4 weeks few side effects were observed. Non-rotatory dizziness was experienced by 5 patients, but one complained of dizziness in the erect position. Complaints of dry mouth, itching, headache and constipation occurred with equal frequency during the placebo and the treatment period (163 ). When labetalol was given intravenously to 16 patients the blood pressure in 3 fell rapidly this was accompanied by transient nausea, faintness and symptoms of pallor and sweating (164 ). 

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