Presynaptic P1-purinoceptors in jejunal branches of the rabbit mesenteric artery and their possible function.
1. Excitatory junction potentials (EJPs) evoked by nerve stimulation with fifteen pulses at 1 Hz were recorded from smooth muscle cells of the rabbit isolated mesenteric artery. The effects of P1-purinoceptor agonists and antagonists, as well as of substances which interfere with the inactivation of endogenous adenosine, were tested. 2. Adenosine and its analogues depressed the EJPs in the train in a concentration-dependent manner. The percentage inhibition of the first EJP and that of the later ones was similar; some early EJPs, however, were inhibited more markedly. The rank order of potency of the agonists was (-)-N6-(R-phenylisopropyl)-adenosine (R-PIA) congruent to 5'-N-ethylcarboxamidoadenosine (NECA) greater than (+)-N6-(S-phenylisopropyl)-adenosine (S-PIA) greater than adenosine. The respective IC40 values (the concentrations producing 40% inhibition of the first EJP in the train) were 0.018, 0.028, 0.83 and 4.7 mumol/l. 3. Three methylxanthines, namely 8-phenyltheophylline (1, 10 mumol/l), 8-cyclopentyltheophylline (0.1, 1 mumol/l) and 8-(p-sulphophenyl)-theophylline (100 mumol/l), antagonized the effect of R-PIA (0.1 mumol/l). When given alone they also enhanced the amplitudes of all EJPs in the train. The percentage facilitation of the first EJP and that of the later ones was similar. Some early EJPs, however, were potentiated more markedly. 8-Phenyltheophylline was less potent than 8-cyclopentyltheophylline both in preventing the action of R-PIA and in enhancing the EJPs. A concentration (100 mumol/l) of 8-(p-sulphophenyl)-theophylline, which strongly antagonized the R-PIA effect, produced only a moderate facilitation of EJPs. 4. S-(p-nitrobenzyl)-6-thioguanosine (10 mumol/l) both depressed the EJPs, and enhanced the inhibitory effect of adenosine. Adenosine deaminase (10 micrograms/ml) caused some potentiation of EJPs; this action was prevented by a concentration (10 mumol/l) of deoxycoformycin, which had no effect of its own. AH21-132 (10 mumol/l) enhanced all EJPs in the train. 5. None of the above substances influenced the resting membrane potential of the smooth muscle cells. In addition, R-PIA (0.1 mumol/l) did not change the depolarization induced by noradrenaline (3 mumol/l). 6. We suggest that the axon terminals of postganglionic sympathetic neurones in the rabbit mesenteric artery possess P1-purinoceptors of the A1-type. The activation of these presynaptic receptors by endogenous adenosine may inhibit the release of the main neuroeffector transmitter, which is probably ATP.(ABSTRACT TRUNCATED AT 400 WORDS)
Illes
P
P
Department of Pharmacology, University of Freiburg, F.R.G.
Jackisch
R
R
Regenold
J T
JT
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007583:Jejunum / Q000098:blood supply; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation; D009131:Muscle, Smooth, Vascular / Q000294:innervation*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011817:Rabbits; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology
D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D013872:Thionucleosides; D006151:Guanosine; C002121:6-(4-nitrobenzylthio)guanosine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D013806:Theophylline; D000243:Adenosine Deaminase; D000241:Adenosine