Table 3.

Some of the pathological manifestations due to heterodimerization of GPCRs.

S. No	Disease	Receptors involved	Molecular mechanism	References
1.	Asthma	EP1/B2AR	⁶Monomeric EP1 receptor has no physiological importance. ⁶Heterodimerization causes modulation of coupling between Gas and β2AR in airway smooth muscle leading to reduced bronchodialatory potential of agonist. ⁶Activation of EP1 receptors increases the downregulation of the heterodimer pair.	McGraw DW et al., 2016
2.	Cardiac failure	AT1R/β-AR	⁶β-ARs antagonist blocks Ang II mediated pathways via trans-inhibition. ⁶Catecholamine-mediated heart rate is regulated by AT1R/β2-AR. ⁶AT1R/β2-AR and β1AR/β2-AR heterodimer regulates cardiac contractility.	Barki-Harrington L et al., 2003; Barki-Harrington L et al., 2003
3.	Preeclampsia	AT1R/B2R	⁶AT1R-mediated hyper-responsiveness in hypertension during pregnancy may cause preeclampsia. ⁶Ang II mediated signaling negatively regulates selective inhibition of heterodimer	Quitterer U et al., 2004; AbdAlla S et al., 2005
4.	AIDS	CCR2/CCR5/CXCR4	⁶Heteromerization between the CCR2 mutant (CCR2V64I) with CXCR4 affects reduced levels of CXCR4 in PBMC and delayed the progression of the disease.	Mellado M et al., 1999; Lee B et al., 1998
5.	Parkinson disease	A2aR/D2R	⁶A2aR agonist regulates cell surface expression of D2R causing decreased binding affinity for D2R agonist.	Fuxe K et al., 2005 and 2007

EP1: prostaglandin E1 receptor.