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Receptors for ATP in rat sensory neurones: the structure‐function relationship for ligands
Author(s) -
Krishtal Oleg A.,
Marchenko Sergey M.,
Obukhov Alexander G.,
Volkova Tatyana M.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11739.x
Subject(s) - agonist , adenosine , chemistry , adenylyl cyclase , adenosine triphosphate , receptor , cytidine , adenosine diphosphate , adenosine a1 receptor , adenosine a2b receptor , biochemistry , stereochemistry , biophysics , adenosine receptor , biology , medicine , platelet , enzyme , platelet aggregation
1 The pharmacological properties of the ATP‐activated conductance in isolated sensory neurones of the rat were investigated by use of voltage clamp and concentration clamp techniques. 2 Adenosine 5′‐triphosphate (ATP), adenosine 5′‐diphosphate (ADP), cytidine 5′‐triphosphate (CTP), cytidine 5′‐diphosphate (CDP) and some derivatives activate these receptors, whereas adenosine 5′‐monophosphate (AMP), cytidine 5′‐monophosphate (CMP) and other naturally‐occurring nucleotides are competitive blockers. 3 In the sequence of substances, adenosine 5′‐(β,γ‐methylene)‐triphosphonate (APPCP), adenosine 5′‐(β,γ‐difluoromethylene)− triphosphonate (APPCF2P), adenosine 5′‐(β,γ‐dichloromethylene)‐triphosphonate (APPCC12P) and adenosine 5′‐(β,γ‐dibromomethylene)triphosphonate (APPCBr2P), the properties of ligands depend on the radius of the atom linked to the carbon of the diphosphonate group. Thus, APPCP is an agonist, APPCF2P is a partial agonist, while dichloromethylene and dibromomethylene analogues of adenosine 5′‐(β,γ‐methylene)triphosphonate demonstrate features of competitive blockers. APPCC12P is the most effective blocker of ATP‐receptors (inhibition constant K i = 21 ± 4μ m ). An adenosyl or adenylyl radical, when connected to the terminal phosphate of ATP, converts the agonist into a partial agonist. 4 Two especially important parts of the ATP molecule are crucial for the interactions with receptors. They are: (1) the vicinity of C6 of the purine ring and (2) the polyphosphate chain. Some modifications in these regions of the molecule result in the transformation of an agonist into an antagonist.