P Adrenergic receptor

Key Words a,-Adrenergic receptor a2-adrenergic receptor P-adrenergic receptor classification function history molecular cloning pharmacology radioligand binding structure. 

RNHCH.CH(OHlCH— R R P Adrenergic receptor blocking agents 473... 

The ability of receptors to couple to G-proteins and initiate GTPase activity may also be independent of ligand. Thus, specific mutations in a- and P-adrenergic receptors have led to receptors that mediate agonist-independent activation of adenylyl cyclase (69,70). These mutations presumably mimic the conformational state of the ligand-activated receptor when they are activated conventionally by ligands. 

Aerosol adniinistration of isoproterenol produces a prompt (2—5 minutes) intense bronchodilatation of relatively short (1 h) duration. The lack of P2-selectivity leads, in many cases, to tachycardia and blood pressure elevation. Also, use of isoproterenol, like all other known P-agonists, results in a down-regulation, or desensitization, of P-adrenergic receptors. This desensitization is only partial, and after time (depending on dose, patient, and agent), a stable, less responsive state is achieved in which P-agonists remain effective. Isoproterenol has been widely used for many years. 

Figure 13.3 G protein-mediated activation of adenylate cyclase by hormone binding. Hormone binding on the extracellular side of a receptor such as the P adrenergic receptor activates a G protein on the cytoplasmic ATP side. The activated form of the G protein...

Lefkowitz, R. J., Mullikin, D., and Caron, M. G. (1976). Regulation of P-adrenergic receptors by guanyl-5 -yl imidodiphosphate and other purine nucleotides. J. Biol. Chem. 251 4686-4692. 

The biological actions of adrenaline and noradrenaline are mediated via nine different G-protein-coupled receptors, which are located in the plasma membrane of neuronal and nonneuronal target cells. These recqrtors are divided into two different groups, a-adrenergic receptors and P-adrenergic recqrtors (see P-adrenergic system). 

The distinction between a- and P-adrenergic receptors was first proposed by Ahlquist in 1948 based on experiments with various catecholamine derivatives to produce excitatory (a) or inhibitory (P) responses in isolated smooth muscle systems. Initially, a further subdivision into presynaptic a2- and postsynaptic oq-receptors was proposed. However, this anatomical classification of a-adrenergic recqrtor subtypes was later abandoned. 

Clinically used p-adrenergic receptor antagonists ( P-blockers ) are either px-selective (e.g. bisoprolol, metoprolol, atenolol, betaxolol) or non-selective,... 

Non-selective P-adrenergic receptor antagonists (e.g. propranolol) can suppress tachycardia and tremor in patients with hyperthyroidism or tremor caused by... 

Danner S, Lohse MJ (1999) Regulation of p-adrenergic receptor responsiveness. Rev Physiol Biochem Pharmacol 136 183-223... 

P-Adrenergic receptor 2 Amino acid variants moderately associated with receptor function and agonist induced down regulation. Some variants may predispose to some types of asthma and modulate action of p-2-adrenergic drugs. 

A. Miklavc, D. Kocjan, J. Mavri, J. Roller and D. Hadzi, On the fundamental difference in thermodynamics of agonist and antagonist interactions with P-adrenergic receptors and the mechanism of entropy-driven binding. Biochem. Pharmacol., 40 (1990) 663-669. 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

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