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Diadenosine polyphosphates evoke Ca 2+ transients in guinea‐pig brain via receptors distinct from those for ATP
Author(s) -
Pintor Jesús,
Puche José A.,
Gualix Javier,
Hoyle Charles H. V.,
MirasPortugal Maria Teresa
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.327be.x
Subject(s) - adenosine , suramin , chemistry , adenosine triphosphate , biochemistry , receptor , nucleotide , cerebellum , biology , endocrinology , gene
1 The ability of diadenosine polyphosphates, namely P 1 ,P 2 ‐di(adenosine) pyrophosphate (Ap2A), P 1 ,P 3 ‐di(adenosine) triphosphate (Ap3A), P 1 ,P 4 ‐di(adenosine) tetraphosphate (Ap4A), P 1 ,P 5 ‐di(adenosine) pentaphosphate (Ap5A) and P 1 ,P 6 ‐di(adenosine) hexaphosphate (Ap6A) to evoke Ca 2+ signals in synaptosomes prepared from three different regions of the guinea‐pig brain was examined. 2 In synaptosomal preparations from the paleocortex (cortex), diencephalon/brainstem (midbrain) and cerebellum all the dinucleotides evoked Ca 2+ signals that were concentration dependent over the range 1‐300 μ m . ATP and its synthetic analogues,α,β‐methylene ATP, 2‐methylthio ATP and adenosine 5‘‐ O ‐(2‐thio)diphosphate (all 100 μ m ) also evoked Ca 2+ signals in these preparations. 3 In the midbrain and cerebellum preparations, responses to ATP and its analogues were attenuated or abolished by the P2 receptor antagonist suramin (100μ m ) but responses to the dinucleotides were not. Also, desensitization by a dinucleotide blocked responses to dinucleotides but not mononucleotides, and desensitization by a mononucleotide blocked responses to mononucleotides but not dinucleotides. 4 In cortical preparations, suramin (100μ m ) blocked responses to both classes of nucleotides. Furthermore, there was mutual cross‐desensitization between the mono‐ and dinucleotides. 5 The adenosine A 1 receptor antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine, did not affect responses evoked by the dinucleotides, nor did the pyrimidine UTP. 6 It is concluded that there are specific dinucleotide receptors, activated by diadenosine polyphosphates, but not ATP or UTP, on synaptic terminals in guinea‐pig diencephalon/brainstem and cerebellum. These receptors bear a similarity to the dinucleotide receptor (P 4 receptor) in rat brain. In guinea‐pig cerebral cortex synaptosomes, diadenosine polyphosphates appear to act via the same receptor as ATP.