Several possibilities could explain the difference in expression of the various adenosine receptor subtypes.
The identification of the various nicotinic receptor subtypes, when coupled with the recent development of three-dimensional structures of surrogate extracellular receptor domains, offers new opportunities to design nicotinic ligands.
Since then, the role of different subtypes of P2 receptors has been elucidated in different pain modalities, amongst which, the role of P2X3, and various P2Y receptor subtypes have already been proposed and examined in cellular and animal models of migraine [19 24].
Along with the divergence of the vasopressin/oxytocin peptides their receptors developed co-evolutionary and in mammals at least two of the various vasopressin receptor subtypes and one oxytocin receptor became established within all the genomes investigated so far.
Alternatively, the difference might be attributed to the activation of different signaling pathways with differing kinetics, especially regarding their affinities to the various NMDA receptor subtypes, e.g., the differences seen with NR1-NR2B aNR1-NR2AR2A activation [51], [52], [53].
Therefore, synthetic somatostatin analogues (SSAs) have been developed that provide prolonged activity while maintaining moderate- or high-affinity binding to various somatostatin receptor subtypes [ 2].
Which of the multiple pathways or which combination thereof emanating from the various EP receptor subtypes is responsible for the pro-carcinogenic effects of PGE2 is far from being understood.
