Fi -adrenergic receptors

Wagoner LE, Craft LL, Zengel P, McGuire N, Rathz DA, et al. 2002. Polymorphisms of the /fi-adrenergic receptor predict exercise capacity in heart failure. Am. Heart J. In press... 

Understanding the pharmacological properties of sympathomimetics and their antagonists depends on knowledge of the classification, distribution, and mechanism of action of a and fi adrenergic receptors (see Tables 6-1, 6-6, 6-7, Figure 10-1, and Table 10-6). 

The antihistamine hydroxyzine is an effective antianxiety agent, but only at doses (-400 mg/day) that produce marked sedation (see Chapter 24). Propranolol and metoprolol, lipophilic fi adrenergic receptor antagonists that enter the CNS, can reduce the autonomic symptoms (nervousness and muscle tremor) associated with specific situational or social phobias but do not appear to be effective in generalized anxiety or panic disorder (see Chapter 10). Similarly, other antiadrener-gic agents, including clonidine, may modify autonomic expression of anxiety but are not demonstrably usfful in the treatment of severe anxiety disorders. 

Theophylline, a methylxanthine, still is commonly used for asthma pharmacotherapy in many countries. In developed countries, the advent of inhaled glucocorticoids, fi adrenergic receptor agonists, and leukotriene-modifying drugs has diminished theophylhne use significantly, and it has been relegated to a third- or fourth-line treatment in patients whose asthma is otherwise difficult to control. 

The most frequently used antiadrenergic drugs for hypertension therapy are the fi-adrenoblockers. Despite the fact that they have been used for many years, their mechanism of action is not completely understood. Only one thing is clear—they are competitive antagonists of adrenaline and noradrenaline on cardiac j3-adrenergic receptors. 

There are two kinds of catecholamine receptors, the a and fi receptors. The former respond best to norepinephrine, whereas the latter prefer epinephrine. Norepinephrine is normally associated with neurotransmission, and a-adrenergic receptors are indeed found in tissues serviced by the sympathetic nervous system. An example is the smooth muscle, which contracts in response to stimulation by... 

Biochemical and biophysical characterization of rhodopsin and the adrenergic receptors have identified residues near the cytoplasmic ends of TMIII and TMVI as important constraints on receptor structure and function. In the rhodopsin structure, the conserved E/DRYmotif found in TMIII is a central feature of the interface with TMVI. This structural motif in TMIII has been referred to as a functional microdomain because of its demonstrated functional significance in numerous GPCRs including the fi opiod receptor, 5-hydroxytryptamine2A receptor, ml muscarinic... 

A target cell is equipped with specific receptors that enable it to recognize and bind a hormone selectively and preferentially. Usually there is one type of receptor for a hormone, but in some cases more than one type of receptor may exist. For example, a -, fi-, and y32-adrenergic receptors are available for catecholamines. The number of receptors for a given hormone in a given cell varies from about 10,000 to more than 100,(XX). 

NONVASCULAR SMOOTH MUSCLES The effects of Epi on smooth muscle depend on the types and densities of adrenergic receptors expressed by the muscle (see Table 6-1). In general, Epi relaxes G1 smooth muscle, due to activation of both a and fi receptors. Intestinal tone and the frequency and amplitude of spontaneous contractions are reduced. The stomach usually is relaxed. By contrast, the pyloric and ileocecal sphincters are contracted (but these effects depend on the preexisting tone of the muscle if tone already is high, Epi causes relaxation if low, contraction). 

PHARMACOLOGICAL EFFECTS The fi blockers vary in their lipid solubility, selectivity for the /Ij adrenergic receptor subtype, presence of partial agonist or intrinsic sympathomimetic activity, and membrane-stabilizing properties. While all of the P receptor antagonists are effective... 

WB 4101 and pH]-5-methylurapidil can only be used to label fi-HTj receptors if Oi-adrenergic receptors are blocked in order to use [ H]-NAN-190 not only aj-adrenergic but also dopamine-Dj receptors need to be blocked. Dopamine-D2 receptors also have to be blocked to allow the use of pH]-spiroxatrine or PH]-buspirone. pH]-Rauwolscine not only has a modest potency (about 1/10 of DPAT), but it is also necessary to block Oj-adrenergic receptors. 

Adrenergic Receptors Cell-surface receptors that bind epinephrine and norepinephrine. There are several different types with somewhat different ligand specificities and effects. (The term comes fi om adrenaline, the old name for epinephrine.)... 

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