caa a22 4500 469079371 CHVBK 20180323132945.0 cr unu---uuuuu 170328e19920401xx s 000 0 eng 10.1007/BF00176619 doi (NATIONALLICENCE)springer-10.1007/BF00176619 Purinoceptor-mediated modulation by endogenous and exogenous agonists of stimulation-evoked [3H]noradrenaline release on rat iris [Elektronische Daten] [H. Fuder, A. Brink, M. Meincke, U. Tauber] Summary: To investigate whether endogenous purinoceptor agonists affect the sympathetic neurotransmission in the rat isolated iris, and to classify the purinoceptors modulating exocytotic [3H]-noradrenaline release, we have determined the effect of adenosine receptor antagonists on, and the relative potency of selected agonists in modulating, the field stimulation-evoked (3 Hz, 2 min) [3H]-noradrenaline overflow. In addition, the apparent affinity constants of 8-phenyltheophylline (8-PT) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in antagonizing the prejunctional effects of purinoceptor agonists were estimated. The relatively A1-selective DPCPX 10 and 100 nmol/l increased the evoked [3H]-noradrenaline overflow by about 25%-35%a indicating a minor inhibition of evoked release by endogenous purinoceptor agonists probably via an A1 adenosine receptor. Whereas the A1/A2-antagonist 8-PT failed to increase the evoked [3H]-noradrenaline overflow in the absence of exogenous agonists (without or with dipyridamole 1 pmol/l present), the relatively A2-selective antagonist CP-66,713 (4-amino-8-chloro -1-phenyl(1,2,4)triazolo(4,3-a)quinoxaline) 100 nmol/l decreased it by 20%-30% in the absence and continuous presence of DPCPX. This may be compatible with a minor A2-mediated facilitation by an endogenous purinoceptor agonist. All exogenous agonists tested (except UTP 100 μmol/l) inhibited the evoked [3H]-noradrenaline overflow. The relative order of agonist potency (IC4o, concentration in μmol/l for inhibition of evoked release by 40%) was CPA (N6-(cyclopentyl)adenosine, 0.004) > R-PIA (R(−)N6-(2phenylisopropyl)adenosine, 0.066) = CHA (N6-(cyclohexyl)adenosine, 0.082) > NECA (N5-(ethyl-carboxamido)adenosine 0.44) > ADO (adenosine, 4.1). ATP was n early equipotent with ADO. Maximum inhibition was 70%-80% and similar for all agonists. Adenosine deaminase 1 u/ml failed to affect the ATP-induced, but abolished the adenosine-induced prejunctional inhibition. The adenosine uptake inhibitor S-p-nitrobenzyl-6-thioguanosine (NBTG) failed to enhance the potency of ADO and ATP. The A1-selective antagonist DPCPX 10 nmol/l did not reduce the ATP potency indicating an effect of ATP per se not mediated via an A1 purinoceptor. Prejunctional affinity constants of 8-PT were 6.07 when tested against adenosine (in the presence of dipyridamole), and 6.60 against CHA. The apparent -log KB of DPCPX tested against CPA was 9.71. The high DPCPX affinity is compatible with an A1 adenosine receptor mediating inhibition of sympathetic neurotransmission in rat iris. This receptor may not be the only prejunctional purinoceptor on rat iris sympathetic nerves. The receptor by which ATP acts prejunctionally in this tissue remains to be determined. Springer-Verlag, 1992 [3H]-noradrenaline release from rat iris nationallicence Purinoceptor-mediated modulation nationallicence Prejunctional A1 adenosine receptor nationallicence DPCPX nationallicence ATP nationallicence Fuder H. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut Brink A. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut Meincke M. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut Tauber U. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 417-423 0028-1298 345:4<417 1992 345 210 https://doi.org/10.1007/BF00176619 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00176619 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fuder H. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut NATIONALLICENCE 700 1- Brink A. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut NATIONALLICENCE 700 1- Meincke M. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut NATIONALLICENCE 700 1- Tauber U. Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Strasse 67, W-6500, Mainz, Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 417-423 0028-1298 345:4<417 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer