TABLE 32-3

The Catecholamine Receptors

Receptor

Relative

Subtype-Specific

Subtype-Specific

Physiologic

Effect

Subtype1

Affinity2

Agonist

Antagonist

Post-receptor Events

Tissue

Ligand3

D1

DA»E=NE

Metoclopramide

Gs: AC stimulation

Vascular smooth muscle (kidney,

DA

Relaxation (low levels)

Increased cAMP

coronary, mesenteric)

Inhibition of prolactin release

D2

DA»E= NE

Bromocriptine

Gi: AC inhibition

Lactotrope (anterior pituitary)

DA

Decreased cAMP

a l

4

E>NE»I

Methoxamine

Phentolamine

Gp:PLC:IP3:DAG

Vascular smooth muscle (skin)

NE

Constriction

Phenylephrine

Phenoxybenzamine

Ca

+2

-Protein Kinase

Vascular smooth muscle (arterioles)

NE

Constriction

Vascular smooth muscle (abdominal

NE

Constriction

viscera except liver)

Intestinal smooth muscle

NE

Relaxation

Intestinal sphincters

NE

Contraction

Urinary smooth muscle

NE

Increased ureter tone, contraction of

(ureter, sphincter of bladder)

sphincter

Iris (radial muscle)

NE

Contraction (mydriasis (pupil dilation))

Skin (piloerector muscle)

NE

Contraction (pilorection)

Skin (sweat gland) (palm of hands,

NE

Secretion

a 2 6

sole of feet

)5

Hypothalamus

NE

Stimulation of ADH release

E> N E » I

Clonidine

Yohimbine

Gi:AC inhibition

ß

cell Islet of Langerhans

NE, E

Inhibition of insulin secretion

Decreased cAMP

Vascular smooth muscle (skin)

E

Constriction (vasoconstriction)

Vascular smooth muscle (veins)

NE, E

Constriction

Hypothalamus

NE

Decreased SRIH and/or increased

GRH release (results in increased

GH release from pituitary)

ß C

I>E= NE

Dobutamine

Metoprolol

Gs: AC stimulation

Heart (SA node, AV node,

NE, E

Increased firing rate; increased

Atenolol

Increased cAMP

His-Purkinjie system, ventricles)

conduction velocity; increased

contractility, increased heart rate,

increased cardiac output

Juxtaglomerular appartus of kidney

NE

Stimulation of renin release

Adipose tissue (white)

E

Lipolysis

ß 2

I>E»NE

Terbutaline

Butoxamine

Gs: AC stimulation

Vascular smooth muscle (skeletal

E

Relaxation (vasodilation)

Salbutamol

Soterenol

Increased cAMP

muscle)

Vascular smooth muscle (coronary)

E

Relaxation (vasodilation)

Bronchiolar smooth muscle

E

Relaxation (bronchodilation)

Skeletal muscle

E

Glycogenolysis; Increased contractility?

a cells Islets of Langerhans

Intestinal smooth muscle

NE, E

Stimulation of glucagon release

Genitourinary smooth muscle

Liver

E

Glycogenolysis; Gluconeogenesis

ß 3

1= NE>E, Low

Fenoterol

none

8

Gs: AC stimulation

White adipose tissue

NE, E

Lipolysis

affinity receptor

Increased cAMP

(visceral > subcutaneous)

Brown adipose tissue

NE(andE) Thermogenesis

'cd and a 2 each have 3 subtypes, information about which can be found in: Bylund (1992) Subtypes of al- anda2-adrenergic receptors. FASEB J 6:832-839.

2DA = dopamine; E = epinephrine; NE = norepinephrine; I = isoproterenol (a non-selective /3-adrenergic agonist; stimulates all 3 subtypes of /3-adrenoceptors).

3NE = norepinephrine as neurotransmitter released from sympathetic nerve endings at synaptic junctions, acting upon postjunctional adrenergic receptors; E = plasma-bome epinephrine that bind to extrajunctional adrenergic receptors that are not

associated with nerve terminals.

4Localized entirely postsynaptically

5Most of the sweat glands are innervated by

c h o lin e r g ic

sympathetic fibers that release AChol at synaptic junctions and respond to sympathetic stimulation with an increase in secretion (increased sweating).The exceptions are the sweat glands in

the palm of the hands and sole of the feet, which are innervated by adrenergic fibers that release NE at synaptic junctions. Emotional excitement activates these adrenergic nerves, and causes sweating in the hands and feet (“adrenergic sweating”).

Emotional excitement usually has no effect on sweating in other regions because the cholinergic sympathetic nerves are mainly controlled by the thermoregulatory center of the hypothalamus, and are not affected by behavioral reactiveness. Note,

however, that all sweat glands haveal adrenoceptors, and are therefore capable of responding to plasma epinephrine (and NE?) with an increase in sweat secretion. This would result in a more generalized sweating.

6Located both pre- and postsynaptically.

Primarily involved in neuronal functions.

8Metoprolol is a non-selective antagonist.