Adrenergic Receptors

Question 1

Maqbool, 1999

Answer 1

B1-AR Arg 389 polymorphism exists in the 4th intracellular loop in a region important for coupling to Gs
In Vitro experiments show Arg389 has higher basal sympathetic activity and higher affinity for Gs compared with Gly389
So Arg389 is HYPERFUNCTIONAL

Question 2

Johnson, 2003

Answer 2

Metoprolol study showed Arg389 homozygotes had 3-fold greater reduction in diastolic BP than Gly389

Question 3

Terra, 2005

Answer 3

Heart failure patients with Arg389 showed greater improvements in LV remodelling with beta-blocker therapy

Question 4

McNamara, 2008

Answer 4

The BEST trial showed that Arg389 patients on beta-blockers showed greater survival and fewer hospital admissions

Question 5

Small, 2000

Answer 5

a2c 322-325 deletion caused decreased coupling to Gi so there is less inhibition
a2c 322-325 is HYPOFUNCTIONAL
Homozygosity for Arg389 and a2c 322-325 deletion increases risk of developing heart failure by 10 fold due to the net effect of both polymorphisms causing increased symptathetic activity

Question 6

Robinson and Hudson, 1998

Answer 6

Additional B4-subtype signalling has been identified in cardiac tissue with low affinity for noradrenaline and adrenaline, but the function of this receptor is unclear