1.4.1 The Adrenergic System

The term adrenoceptor was first introduced by AHLQUIST to explain the different physiological effects of catecholamines [69]. In 1948 Ahlquist  [70] described the initial subclassification of adrenoceptors into α- and β-receptors on the basis of their pharmacological characteristics. For his study he used the agonists epinephrine, norepinephrine and isoprenaline. He showed that this substances always lead to a constriction of the smooth muscles of arterioles, the uterus and M. dilatator pupillae in the same order of effectiveness: L(–)-epinephrine L(–)-norepinephrine isoprenaline (α-receptors). The vasodilatatory effect and the positive chronotropic effects (i.e., rise of heart rate) follow the order isoprenaline > L(–)-epinephrine L(–)-norepinephrine (β-receptors).

He postulated that the effects of these sympathomimetics are mediated by different receptors:

These types of receptors were further splitted into several subgroups. Table 1.4 summarises their pharmacological differentiation and physiological effects.

The existence of these receptor subtypes has been proven by radioligand assays. It has been shown, that a number of tissues may contain both β-receptors. This distribution is often unbalanced, as table 1.3 shows.


Tissue: β1-subtype β2-subtype
   
heart
atrium 70% 30%
ventricle 80% 20%
kidney 70% 30%
placenta 50% 50%
lungs 30% 70%
liver 100%
vena saphena 100%
leukocytes 0% 100%
platelets 0% 100%
erythrocytes 0% 100%(?)

Table 1.3: Distribution of β-receptors in human tissue



 
α1-adrenoceptors

Selective agonists: phenylephrine, methoxamine, amidephrine, cirazoline

Selective antagonists: prazosin, terazosin, BE 2254

Occurrence and effects: salivary glands (stimulation of K+ and H 2O secretion), smooth muscles of arterioles (constriction) and bronchi (contraction), uterus, sphincters of the digestive system and the bladder, musculus dilatator pupillae (contraction).

 
α2-adrenoceptors

Selective agonists: α-methyl-arterenone , B-HT 920, B-HT 933

Selective antagonists: yohimbine, rauwolscine, RX 781094

Occurrence and effects: presynaptical membranes (decreases via a feedback the release of norepinephrine), parotis, pancreas (decreases insulin secretion), uterus, kidney (decreases renin secretion), central nervous system, fat cells (decreases lipolysis), platelets (aggregation).

 
β1-adrenoceptors

Selective agonists: norepinephrine

Selective antagonists: practolol, metoprolol, atenolol, bisoprolol, betaxolol, CGP 20712A

Occurrence and effects: heart muscle (positive chronotrope, dromotrope and inotrope), kidney (increased renin secretion), salivary glands (increased amylase secretion).

 
β2-adrenoceptors

Selective agonists: salbutamol, fenoterol, terbutaline, procaterol

Selective antagonists: ICI 118, ICI 551

Occurrence and effects: vascular system and bronchi (dilatation), digestive system (relaxation of intestine mobility), fat cells (lipolysis), liver (increase of glycolysis and gluconeogenesis), muscles (increase of glycolysis), pancreas (increase of insulin and glucagon secretion)



Table 1.4: Pharmacological and physiological properties of adrenergic receptors

© 2001 Alexander Binder