Adrenergic Drugs I Flashcards
adrenergic receptors are _
GPCR’s
alpha-1 receptors
Gq phosphorylates alpha subunit –> beta-gamma detach –> Galpha-Pi activates PLC –> PLC cleaves PIP2 into DAG and IP3 (2nd messengers)
alpha-1 receptor functions
vasoconstriction, smooth muscle relaxation, contraction of GI tract, increase heart force, and stimulates glygenolysis/gluconeogenesis
muscle contraction by alpha-1 receptors
increases intracellular [Ca++] via release of intracellular stores –> calmodulin activation –> phosphorylation of MLCs
alpha-2 receptors
activation of Gi
Gi protein
inhibits adenylyl cyclase, reducing cAMP; also activates K+ channels for repolarization
alpha-2 receptor functions
contraction of smooth muscle, decreases insulin secretion, decreases NE release
beta-receptors
activate Gs which activates adenylyl cyclase
beta-1 receptors
in heart, kidneys, and adipocytes; produce positive inotropic and chronotropic effect
beta-2 receptors
in heart, vascular, bronchial and GI smooth muscle, glands, leukocytes, hepatocytes; smooth muscle relaxation
beta-3 receptors
in adipose tissue and GI tract; metabolic effects
beta receptors are found on _
post-synaptic cells
alpha-2 receptors are found on _
pre or post-synaptic cells
alpha-1 receptors are found on _
post-synaptic cells
beta-1 effects
tachycardia, increased renin, increased myocardial contractility
beta-2 effects
vasodilation, decreased peripheral resistance, bronchodilation, increases glucagon, increases glycogenolysis
signal termination steps
desensitization –> sequestration –> recycling/degradation
desensitization
ligand binding promotes phosphorylation of receptor –> beta-arrestin will bind –> now less sensitive to hormones or NTs binding
sequestration
after beta-arrestin binds, clathrin-coated vesicles will form –> pulls receptor away from membrane
catecholamines
dopamine, norepinephrine, epinephrine
high dose epinephrine
increase vasoconstriction, increase inotropy, increase chonotropy, increase HR and BP
low dose epinephrine
vasodilation, increase inotropy and chonotropy so still increases HR and CO (increased to overcome vasodilation)
at low doses epinephrine will bind _
beta receptors which allows vasodilation
at high doses epinephrine binds _
alpha receptors which causes vasoconstriction (lower affinity for alpha than beta)
