Table 1.

Splice variation and potential physiological roles of receptor isoforms

Receptor	Event description	Potential physiological relevance	References
5-HT receptors	Several	Various	Reviewed in [19] and [20]
Muscarinic acetylcholine receptor	Novel intron/exon	Unknown	[21]
Adenosine receptors	5′-UTR splicing; novel exons	Differential translation	[21, 22]
α1-Adrenoceptors	Several	Various	Reviewed in [23]
Angiotensin-II receptor	Exon inclusion/exclusion	Distinct signalling properties	[24, 25]
Calcitonin receptor	Exon exclusion-headless variant	Abolished ligand binding/dominant-negative effect	[26, 27]
Cannabinoid receptor type 1	Alternative donor/acceptor site	Altered pharmacology	[28, 29]
Chemokine receptor (CXCR3)	Novel acceptor site-distinct N-terminus	Distinct signalling properties	[30]
Cholecystokinin receptor (CCK-B)	Intron inclusion	Constitutively active, ligand–independent Src activation	[8, 31, 32]
Corticotropin-releasing hormone receptors (type 1 and 2)	Several	Various	[33–35]
Dopamine receptor (D2)	Exon inclusion/exclusion	Distinct signalling properties and cellular localisation	[36, 37]
Dopamine receptor (D3)	Premature stop codon-lacks TM6 and TM7	Distinct cellular localisation	[38]
Endothelin B receptor	Exon exclusion	Not transcribed	[39]
Epidermal growth factor-seven TM receptor	Trans-splicing	Diversification of ligand repertoire	[40]
Follicle-stimulating hormone receptor	Exon exclusion and used of additional exon	Not GPCR, but growth factor receptor	[41]
GABAB receptor	Several	Various	Reviewed in [42]
Gastric inhibitory polypeptide receptor	Intron retention-premature stop codon	Impaired signalling; dominant-negative effect	[43]
Growth hormone-releasing hormone receptor	Exon exclusion, intron retention	Impaired signalling; dominant-negative effect	[44–49]
Histamin receptors (H3 and H4)	Several	Various	[50–52]
Leukotriene B4 receptor	Alternative donor/acceptor sites, novel exons/introns	Unknown	[21]
Luteinizing hormone receptor	Mutation at the intron 10/exon 11, resulting in 8 aa deletion	Abolished reproduction	[53, 54]
Melanocortin 2 receptor	5′-UTR splicing	Adipogenesis?	[55]
Metabotropic glutamate receptors	Alternative C-terminal exons	Distinct signalling; role in development	[56–58]
Neurokinin receptor 1	Exon exclusion- truncation	Distinct signalling; role in immunomodulation	[59–64]
Neurokinin receptor 2	Exon exclusion	Impaired ligand binding and signalling	[65, 66]
Neuropeptide S receptor (GPRA)	Alternative C-terminal exons, truncation	Intracellular localisation of truncated isoform	[67]
Opioid receptors	Several	Various	Reviewed in [68]
Parathyroid hormone (-related peptide) receptor	5′-UTR; exon exclusion	Lack of post-translational glycosylation	[14, 69]
Prostaglandin receptors	Several	Various	[70–72]
Relaxin receptors	Several	Various	[73–75]
Secretin receptor	Exon exclusion	Unknown—cancer biology?	[76, 77]
Somatostatin receptor (sst2)	Exon exclusion-truncation	Altered desensitisation	[78], reviewed in [79]
Thromboxane receptors	Alternative C-terminal exons	Distinct internalisation/interaction with arrestins	[80, 81]
Vasopressin V2 receptor	Alternative splice site	Dominant-negative effect	[82, 83]
VIP and PACAP receptors	Several	Various	Reviewed in [84]

Numerous splicing events that affect the expression of GPCRs mRNA and protein have been described since 2001 (for splice variants known before 2001, see [17, 18]). Over-expression studies provide valuable insights into potential physiological relevance of these events, although in many cases the real physiological roles in endogenous systems are unknown