Premium
A novel receptor for diadenosine polyphosphates coupled to calcium increase in rat midbrain synaptosomes
Author(s) -
Pintor Jesús,
MirasPortugal M. Teresa
Publication year - 1995
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.1476-5381.1995.tb15894.x
Subject(s) - calcium , midbrain , chemistry , receptor , biochemistry , synaptosome , endocrinology , biophysics , microbiology and biotechnology , biology , central nervous system , organic chemistry
1 Diadenosine polyphosphates, AP 4 A and Ap 5 A, as well as ATP, α,β‐MeATP and ADP‐β‐S, were able to elicit variable intrasynaptosomal Ca 2+ increases in rat midbrain synaptic terminals. The origin of the Ca 2+ increment was the extrasynaptosomal space since the elimination of extracellular Ca 2+ abolished the effect of all the agonists. 2 The P 2 ‐purinoceptor antagonist, suramin, did not affect the Ca 2+ –increase evoked by diadenosine polyphosphates but dramatically blocked the Ca 2+ entry induced by ATP and its synthetic analogues. 3 The actions of Ap 5 A and ATP on the intrasynaptosomal Ca 2+ increase did not cross‐desensitize. 4 Concentration‐response studies for diadenosine polyphosphates showed pD 2 values of 54.5 ±4.2 μm and 55.6 ±3.8 μ m for AP 4 A and Ap 5 A, respectively. 5 The entry of calcium induced by diadenosine polyphosphates could be separated into two components. The first represented a selective voltage‐independent Ca 2+ entry; the second, a sustained phase which was voltage‐dependent. 6 Studies on the voltage‐dependent Ca 2+ –channels involved in the effects of the diadenosine polyphosphates, demonstrated that Ω‐conotoxin G‐VI‐A inhibited the sustained Ca 2+ –entry, suggesting the participation of an N‐type Ca 2+ –channel. This toxin was unable to abolish the initial cation entry induced by AP 4 A or Ap 5 A. Ω‐Agatoxin IV‐A, tetrodotoxin, or nifedipine did not inhibit the effects of the diadenosine polyphosphates. 7 The effect of ATP on Ca 2+ –entry was abolished by nifedipine and Ω‐conotoxin G‐VI‐A, suggesting the participation of L‐ and N‐type Ca 2+ –channels in the response to ATP. 8 These data suggest that AP 4 A, Ap 5 A and ATP activate the same intracellular Ca 2+ signal through different receptors and different mechanisms. AP 4 A and Ap 5 A induce a more selective Ca 2+ –entry in a voltage‐independent process. This is the first time that a selective action of diadenosine polyphosphate through receptors other than P 1 and P 2 ‐purinoceptors has been described.