Epinephrine receptor pharmacology

The physiological effects of the catecholamines are mediated by a large number of different receptors that are of particular interest in pharmacology. Norepinephrine acts in the autonomic nervous system and certain areas of the brain. Epinephrine is also used as a transmitter by some neurons. 

Pharmacology Epinephrine, a direct-acting sympathomimetic agent, acts on and receptors. Topical application, therefore, causes conjunctival decongestion (vasoconstriction), transient mydriasis (pupillary dilation), and reduction in intraocular pressure (lOP). It is believed lOP reduction primarily is caused by reduced aqueous production and increased aqueous outflow. The duration of decrease in lOP is 12 to 24 hours. 

IgE-medlated release of mast cell contents. Inset, Intact mast cell with histamine stored In granules. An IgE antibody molecule Is depicted adjacent to the mast cell. Two IgE molecules combine with a mast cell (sensitization). The attachment of an antigen (allergen) to the sensitized mast cell Initiates release of histamine (and other substances) from the mast cell. This degranulation can be prevented by such agents as isoproterenol, theophylline, epinephrine, and cromolyn sodium. H antihistamines do not interfere with degranulation but instead prevent actions of histamine at various pharmacological receptors. 

Weiner, N. (1991) Drugs that inhibit adrenergic nerves and block adrenergic receptors. In Gilman, A. and Goodman, L., eds. Norepinephrine, Epinephrine and the Sympathomimetic Amines, 7th ed. New York The Pharmacological Basis of Therapeutics, pp. 145-180. 

Adrenoreceptors were initially characterized pharmacologically, with receptors having the comparative potencies epinephrine > norepinephrine >> isoproterenol, and receptors having the comparative potencies isoproterenol > epinephrine > norepinephrine. The development of selective antagonists revealed the presence of subtypes of these receptors, which were finally characterized by molecular cloning. We now know that unique genes encode the receptor subtypes listed in Table 9-1. 

Vascular smooth muscle tone is regulated by adrenoceptors consequently, catecholamines are important in controlling peripheral vascular resistance and venous capacitance. Alpha receptors increase arterial resistance, whereas 2 receptors promote smooth muscle relaxation. There are major differences in receptor types in the various vascular beds (Table 9-4). The skin vessels have predominantly receptors and constrict in the presence of epinephrine and norepinephrine, as do the splanchnic vessels. Vessels in skeletal muscle may constrict or dilate depending on whether ffor 13 receptors are activated. Consequently, the overall effects of a sympathomimetic drug on blood vessels depend on the relative activities of that drug at and 8receptors and the anatomic sites of the vessels affected. In addition, Di receptors promote vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels. Activation of the Di receptors in the renal vasculature may play a major role in the natriuresis induced by pharmacologic administration of dopamine. 

The effect in an anesthetized dog of the injection of epinephrine before and after propranolol. In the presence of a B-receptor-blocking agent, epinephrine no longer augments the force of contraction (measured by a strain gauge attached to the ventricular wall) nor increases cardiac rate. Blood pressure is still elevated by epinephrine because vasoconstriction is not blocked. (Reproduced, with permission, from Shanks RG The pharmacology of b sympathetic blockade. Am J Cardiol 1966 18 312.)... 

Phenylephrine is a synthetic sympathomimetic amine structurally similar to epinephrine. It acts primarily on ai receptors and has little or no effect on (3 receptors. A minor part of its pharmacologic effects may be attributed to release of norepinephrine from adrenergic nerve terminals. 

The toxicities of the beta blockers are directly related to their pharmacologic effects. These agents block the effects of catecholamines such as epinephrine and norepinephrine on the beta-1 and beta-2 receptors. Beta-1 receptors are located in the heart, kidneys, and eyes. Toxicity is most often due to antagonism of the cardiac beta-1 receptors. 

The paradigm used by Ahlquist for classifying receptors based on their pharmacological characteristics (i.e., rank order of potency of agonists) was further developed by Lands and colleagues with the subdivision of the P-adrenergic receptors into pr and P2-subtypes (12). The pradrenergic receptor, the dominant receptor in heart and adipose tissue, was equally sensitive to epinephrine and... 

Adrenergic receptors (ARs) are the interface between the sympathetic nervous system and the cardiovascular system. ARs include two major subtypes, a and P, based on their pharmacological properties and molecular structure. The a-ARs consist of three ar AR subtypes and three o -ARs. P-ARs are also classified into three well-characterized subtypes Pb p2, and P3. Although they respond to the same hormones (norepinephrine and epinephrine), a- and P-ARs differ significantly in the types of cellular responses they mediate. 

FIGURE 1.2 A sampling of the heterogeneous physiological and pharmacological response to the hormone epinephrine. The concept of receptors links these diverse effects to a single control point, namely the P-adrenoceptor. 

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