Adrenergic Receptors..Pharmacology

Two types of receptor sites are theorized to explain adrenergic effects.

Alpha-Receptors

• Alpha-receptors are associated mainly with increased contractibility of vascular smooth muscle and intestinal relaxation.

Alpha1

• The alpha1 is located at postsynaptic effector sites to stimulate transmitter release in smooth muscle. For example, the smooth muscle of peripheral blood vessels is contracted in alpha1 stimulation.

Alpha2

• The alpha2 receptor site is located presynaptic on axon terminals to inhibit the release of nor-epinephrine (the transmitter). The effects of alpha2 stimulation results in relaxation of the intestinal tract--motility and tone are decreased.

Beta-Receptors

• Beta-receptors are associated with vasodilation and relaxation of nonintestinal smooth muscle and cardiac stimulation.
• Beta1 Stimulation of beta1 receptor sites results in cardiac stimulation and lipolysis.
• Beta2 Stimulation of beta2 receptor sites causes bronchodilation, relaxation of blood vessels (usually in skeletal muscles), and muscle glycogenolysis.

Alpha Receptor Site: Important features of the site include in order of importance: An anionic site - which binds the positive ammonium group. One hydrogen bonding area A flat area non-polar area for the aromatic ring. Beta Receptor Site: Important features of the site include in order of importance - also see the graphic on the left: An anionic site - shown as Asp anionic negative acid group which binds the positive ammonium group. Two hydrogen bonding areas - shown as two Serine with alcohol (OH) groups hydrogen bonding to the phenol OH groups of the NE. A flat area non-polar area for the aromatic ring.  Tissue   Receptor Subtype  Agonists  Antagonists  Heart   beta1 NE, EP, dobutamine, xamoterol atenolol, metoprolol.  Adipose tissue   beta1, beta 3? Vascular Smooth Muscle  beta 2  EP, salbutamol, terbutaline, salmeterol butoxamine Airway Smooth Muscle   beta 2  terbutaline, salbutamol, salmeterol and zinterol, butoxamine  Smooth muscle contraction  alpha 1  NE, EP, phenylephrine, oxymetazoline) prazosin, doxazocin  Inhibition of transmitter release Hypotension, anaesthesia, Vasoconstriction  alpha 2 clenbuterol, alpha-methylnoradrenaline, dexmedetomidine, and mivazerol, clonidine, clenbuterol yohimbine, idazoxan, atipamezole, efaroxan, and rauwolscine Receptor Sites  alpha-receptor  beta-receptor  Vasoconstriction  vasodilation (b2)  iris dilation  cardioacceleration (b1)  intestinal relaxation  intestinal relaxation (b2)  intestinal sphincter contraction  uterus relaxation(b2)  bladder sphincter contraction  bronchodilation (b2)