Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides.

Abstract

SUMMARY Adenosine and the adenine nucleotides caused a greater relaxation of strips of canine saphenous vein and tibial artery when they had been contracted by nerve stimulation than by exogenous norepinephrine. An infusion of adenosine into the dogs' lateral saphenous vein, perfused at constant flow, caused a greater relaxation of this vein when constricted by electrical stimulation of the lumbar sympathetic chain than by exogenous norepinephrine. That this difference was due to inhibition by these compounds of the output of neurotransmirter from the sympathetic nerve endings was demonstrated by column chromatographic analysis of the radioactivity in the supervision fluid of vein strips, previously incubated with tritiated norepinephrine. Both adenosine and adenosine triphosphate (10"' M) reduced the efflux of 3 H-norepinephrine during nerve stimulation with electrical impulses. Adenosine also reduced the efflux caused by potassium (30 mM), but not that caused by tyramine (6 x 10~6 M). Theophylline antagonized the inhibitory effect of adenosine on the sympathetic neurotransmission. We found that at 4 x 10 4 M adenosine triphosphate still caused a decreased efflux of neurotransmitter during electrical stimulation, but with adenosine the 3 H-norepinephrine efflux no longer decreased and the overflow of deaminated compounds increased. Furthermore, the same concentration of adenosine increased the efflux of 3 H-norepinephrine and deaminated compounds in unstimulated strips, and the increase of 3 H-norepinephrine was enhanced after monoamine oxidase inhibition. Thus, we conclude that at higher concentrations adenosine increases the intraneuronal leakage of norepinephrine out of the storage vesicles.ADENOSINE and the adenine nucleotides by a local action on blood vessels cause their dilation. This has been demonstrated both in vivo and in vitro. '" 3 There is evidence that these substances can inhibit neuromuscular transmission in the rat phrenic nerve-diaphragm and frog sartorius preparations 4 ' 5 and cholinergic neurotransmission in the intestinal wall. 6 The present experiments were performed to determine whether adenosine and related nucleotides inhibit adrenergic neurotransmission in canine blood vessels. Methods STUDIES IN VITROHelical strips of lateral saphenous veins and anterior tibial arteries, isolated from dogs (15-25 kg) anesthetized with sodium pentobarbital (30 mg/kg, iv), were placed in an organ bath filled with Krebs-Ringer solution (NaCl, 118.2 mM; KC1, 4.7 mM; MgSO 4 , 1.2 mM; KH 2 PO 4 , 1.2 mM; CaCl 2 , 2.5 mM; NaHCO 3 , 25 mM; calcium disodium ethylenediaminetetraacetate (EDTA) 0.026 mM; and glucose, 5.5 mM) maintained at 37°C and aerated with a 95% O 2 -5% CO 2 mixture. The strips were attached to a force transducer (Grass FT 03C) for isometric tension recording. The transducer was mounted on a movable support allowing fine adjustments of the strip length and connected to a pen writing recorder (Gould Brush 220). For electrical stimulation of the preparations, two rectangular platinum electr...

Adenosine Inhibition of Γ‐aminobutyric Acid Release From Slices of Rat Cerebral Cortex

“…This is consistent with the evidence for an inhibition of transmitter release from both peripheral and central cholinergic and adrenergic neurones (Ginsborg & Hirst, 1972;Ribeiro & Walker, 1975;Sawynok & Jhamandas, 1976;Hedqvist & Fredholm, 1976;Vizi & Knoll, 1976;Clanachan et al, 1977;Enero & Saidman, 1977;Gustafsson et al, 1978;Paton et al, 1978). The ability of theophylline to prevent this effect also suggests that a receptor is involved similar to that which has been found to mediate effects of adenosine on transmitter release in other systems (Ginsborg & Hirst, 1972;Sawynok & Jhamandas, 1976;Verhaeghe et al, 1977;Su, 1978) as well as the effects of adenosine on adenylate cyclase (Sattin & Rall, 1970;Blume, Dalton & Sheppard, 1973;Sattin, Rall & Zanella, 1975) depression of neuronal firing (Phillis & Kostopoulos, 1975;Stone & Taylor, 1977;Taylor & Stone, 1978) and vascular tone (Wahl & Kuschinsky, 1976). Further the antagonism by theophylline and the greater potency of adenosine compared with ATP suggests that the receptor involved is that recently classified as PI by Burnstock (1978).…”

“…This action has been studied at both cholinergic (Ginsborg & Hirst, 1972; Ribeiro & Walker, 1975;Sawynok & Jhamandas, 1976;Vizi & Knoll, 1976;Gustafsson, Hedqvist, Fredholm & Lundgren. 1978) and adrenergic (Hedqvist & Fredholm, 1976;Clanachan, Johns & Paton, 1977;Enero & Saidman, 1977;Verhaeghe, Vanhoutte & Shepherd, 1977;Su, 1978;Paton, Bar, Clanachan & Lauzon, 1978) terminals in the peripheral nervous system. It has recently been concluded that adenosine can also reduce acetylcholine release at the synapse between motor axon collaterals and Renshaw cells (Lekic, 1977), and noradrenaline release from terminals in the cerebral cortex in vivo (Taylor & Stone, 1980) and in vitro (Harms, Wardeh & Mulder, 1978 (Bowery & Brown, 1974 …”

Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries.

“…Since the decreases in tension caused by adenosine and AMP were unaffected by the procedure, an explanation could be that, as is presumably the case for the prejunctional inhibitory effect of ATP (Verhaeghe, Vanhoutte & Shepherd, 1977; De Mey, Burnstock & Vanhoutte 1979), ATP (and ADP) must be degraded to adenosine (or AMP) by the endothelial cells in order to exert their inhibitory effect on the vascular smooth muscle cells of the media, but that the latter lack the enzymes necessary for this degradation. This interpretation is hard to reconcile with: (1) the findings that a concentration of theophylline which abolishes the relaxations caused by adenosine does not affect the inhibition evoked by ATP, and (2) the observation that ATP but not adenosine…”

Responses of the aorta of the garter snake (Thamnophis sirtalis parietalis) to purines

“…P2-purinoceptors are described as being preferentially activated by ATP and adenosine 5'-diphosphate (ADP); these were initially divided into P2X and P2Y subgroups, based on potency orders of ATP analogues (Burnstock & Kennedy, been identified (Vials & Burnstock, 1993). Activation of Alpurinoceptors generally mediates prejunctional inhibition of neurotransmitter release (Verhaeghe et al, 1977).…”