Receptors for ATP in rat sensory neurones: the structure‐function relationship for ligands

Oleg A. Krishtal, Sergey M. Marchenko, Alexander G. Obukhov, Tatyana M. Volkova

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

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. 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. 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 Ki = 21 ± 4μm). An adenosyl or adenylyl radical, when connected to the terminal phosphate of ATP, converts the agonist into a partial agonist. 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. 1988 British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)1057-1062
Number of pages6
JournalBritish Journal of Pharmacology
Volume95
Issue number4
DOIs
StatePublished - Dec 1988
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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