Characterization of P2-purinoceptors in the smooth muscle of the rat tail artery: a comparison between contractile and electrophysiological responses.
1. The electrophysiological actions of the P2-purinoceptor agonists, adenosine 5'-triphosphate (ATP), 2-methylthioATP (2-meSATP), alpha, beta-methyleneATP (alpha, beta-meATP) and uridine 5'-triphosphate (UTP) were studied under concentration and voltage-clamp conditions in acutely dissociated rat tail artery smooth muscle cells. For comparison, their actions as vasoconstrictors were studied in intact ring preparations. 2. Rapid application of ATP (100 nM-1 microM) via a U-tube superfusion system activated concentration-dependent inward currents with a latency to onset of less than 3 ms. The inward current decayed by more than 95% during a 2 s application of 300 nM and 1 microM ATP. 3. 2-meSATP (100 mM-1 microM) and alpha, beta-meATP (100 nM-1 microM) also evoked transient inward currents. The agonist order of potency was ATP = 2-meSATP > or = alpha, beta-meATP. UTP (300 nM-1 microM) did not produce a change in the holding current. 4. A second application of ATP (300 nM and 1 microM) 10 min after the first, evoked currents which were one third of the initial amplitude. This decline was dependent upon activation of the P2-purinoceptor. Similar results were seen with 2-meSATP and alpha, beta-meATP (both 300 nM and 1 microM). Cross-desensitization was seen between ATP and 2-meSATP or alpha, beta-meATP. 5. Inward currents evoked by ATP, 2-meSATP and alpha, beta-meATP (all 1 microM) were abolished by the P2-purinoceptor antagonist suramin (100 microM). 6. Alpha, beta-meATP (100 nM-30 micro M), 2-meSATP (3 micro M- 100 micro M), ATP (3 micro M-I mM) and UTP (3 ELM-I mM)produced concentration-dependent contractions of rat tail artery rings. When measured at a level equal to 50% of the maximum response to noradrenaline, the rank order of agonist potency was alpha,beta-meATP>>2-meSATP >UTP >ATP.7. This study shows that the rank order of agonist potency at the P2X-purinoceptor which mediates contractions of the rat isolated tail artery is very different from the potency order for evoking the inward current which initiates the contractions. It is concluded that this difference may be due to the relative absence of breakdown of some of the agonists in the single cell system compared with artery rings.
Department of Physiology and Pharmacology, University of Strathclyde, Royal College, Glasgow.
R J
RJ
Evans
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Kennedy
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D013623:Tail / Q000098:blood supply; D013873:Thionucleotides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D014544:Uridine Triphosphate; C008501:2-methylthio-ATP