A novel P1 purinoceptor activates an outward K+ current in follicular oocytes of Xenopus laevis.
Follicular oocytes of Xenopus laevis possess P1 purinoceptors where, seemingly, both adenosine (Ado) and ATP are agonists. The basis of ATP agonism at this P1 purinoceptor was investigated using electrophysiological and biochemical procedures. Ado and ATP activated an outward K+ current that reversed at -90 mV, was reduced by TEA and was inhibited by theophylline and 8-(p-sulphophenyl)-theophylline but not by suramin. Outward K+ current to ATP and Ado also was inhibited by alpha, beta-methylene ATP. The affinity constants for Ado and ATP were identical, although ATP was a partial agonist. The potency order of nucleosides/nucleotides was 5'-N-ethylcarboxamide- adenosine > Ado > AMP > CGS-21680 > beta, gamma-methylene ATP = ATP > ADP > R-N6 phenylisopropyl-adenosine, whereas 2-methylthioadenosine, ATP-O-(3-thiotriphosphate), uridine 5'-triphosphate and alpha, beta-methylene ATP were inactive. Outward K+ current to ATP and nondegradable Ado analogs was unaffected by adenosine deaminase (although this enzyme prevented Ado agonism), which suggests that ATP is not broken down to Ado before activating K+ channels. The activity of oocyte ecto-ATPase was determined by HPLC analysis of ATP breakdown and by the production of inorganic phosphate. Oocyte ecto-ATPase showed a low rate of ATP hydrolysis and was incapable of generating sufficient Ado/AMP to activate P1 purinoceptors. The results show that a P1 purinoceptor that is not typical of other known Ado receptors (and ATP receptors) is present in the follicle cell layer of Xenopus oocytes and represents a novel purinoceptor subtype where both Ado and ATP are agonists in their own right.
King
B F
BF
Department of Anatomy, University College London, UK.
Pintor
J
J
Wang
S
S
Ziganshin
A U
AU
Ziganshina
L E
LE
Burnstock
G
G
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D009865:Oocytes / Q000502:physiology* / Q000648:ultrastructure; D010710:Phosphates / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014982:Xenopus laevis
D010710:Phosphates; D015221:Potassium Channels; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000241:Adenosine; D011188:Potassium