Indirect evidence that purinergic modulation of perivascular adrenergic neurotransmission in the portal vein is a physiological process

Burnstock, Geoffrey; Crowe, R.; Kennedy, Charles; Török, J

doi:10.1111/j.1476-5381.1984.tb10770.x

Cited by 31 publications

(5 citation statements)

References 33 publications

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“…This confirms findings using dog saphenous vein (Verhaeghe et a/. 1977) as well as rabbit aorta (Su 1978;Husted & Nedergaard 1981) portal vein and ear artery (Su 1978;Burnstock et a/. 1984).…”

Section: Discussionsupporting

confidence: 85%

Dual Inhibitory Action of ATP on Adrenergic Neuroeffector Transmission in Rabbit Pulmonary Artery

Husted¹,

Nedergaard²

1985

Acta Pharmacologica et Toxicologica

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The aim of this study was to determine whether the inhibitory action of ATP on sympathetic neuroeffector transmission in the isolated pulmonary artery is due to ATP itself or one of its dephosphorylated breakdown products, ADP, AMP or adenosine. Furthermore, the mechanism of the inhibitory action was investigated. ATP (10(-6)-3 X 10(-4) M), the degradation-resistant ATP-analogue, beta, gamma-methylene-5'-triphosphate (10(-5)-3 X 10(-4) M), ADP (10(-6)-3 X 10(-4) M), AMP (10(-5)-3 X 10(-4) M), adenosine (10(-5)-3 X 10(-4) M) and 2-chloroadenosine (10(-7)-3 X 10(-4) M) reduced the contractions evoked by field-stimulation. This was also the case for prostaglandin E2 (3 X 10(-9)-3 X 10(-7) M), while prostaglandin F2 alpha (1.4 X 10(-8) M) slightly augmented the neurogenic response. The time course of the inhibitory effect of purinergic compounds on the stimulation evoked contractions was studied. In the case of ATP and ADP the inhibition was biphasic: an initial marked block (1 min. after drug addition) which in the continued presence of either compound recovered partially 10 min. later and then remained almost constant for another 90 min. The other purinergic agents caused a monophasic reduction. In the presence of indomethacin (5 X 10(-5) M), ATP and ADP also reduced the neurogenic contractions in a monophasic manner. Indomethacin did not alter the beta, gamma-methylene-5'-triphosphate-induced inhibition. Dilazep (3 X 10(-6) M) plus deoxycoformycin (3.6 X 10(-6) M), augmented the inhibitory effect of ATP. In contrast, theophylline (5 X 10(-5) M) did not alter the effect of ATP. The inhibitory effect of ATP (10(-4) M) on stimulation-evoked contractions was inversely proportional to the extracellular Ca2+ concentration (0.3-5.2 mM) and to frequency of stimulation (3-15 Hz). These results suggest that ATP initially causes a presynaptic inhibition of noradrenaline release evoked by field-stimulation. This phase I block is probably mainly due to an ADP-mediated short-lasting release of prostaglandins of the E type. The continuous inhibition (phase II) is probably due to ATP and its metabolites, possibly mainly adenosine. The phase II inhibition may possibly involve a decreased entry of Ca2+ into adrenergic nerve terminals during depolarization.

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Section: Discussionsupporting

confidence: 85%

Dual Inhibitory Action of ATP on Adrenergic Neuroeffector Transmission in Rabbit Pulmonary Artery

Husted¹,

Nedergaard²

1985

Acta Pharmacologica et Toxicologica

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“…Release of ATP and/or ADP into the blood can occur through several mechanisms. ATP has been proposed as an autonomic neurotransmitter (Burnstock, 1979(Burnstock, , 1981 and may be released from adrenergic nerves in the portal vein as co-transmitter (Burnstock et al, 1984). Stimulation of human endothelial cells by thrombin causes the selective release of most of the ATP of the endothelial cell (Pearson & Gordon, 1979).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of glycogenolysis by adenine nucleotides in the perfused rat liver

Buxton¹,

Robertson²,

Olson³

1986

Biochemical Journal

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Infusion of adenine nucleotides and adenosine into perfused rat livers resulted in stimulation of hepatic glycogenolysis, transient increases in the effluent perfusate [3-hydroxybutyrate]/[acetoacetate] ratio, and increased portal vein pressure. In livers perfused with buffer containing 50 microM-Ca2+, transient efflux of Ca2+ was seen on stimulation of the liver with adenine nucleotides or adenosine. ADP was the most potent of the nucleotides, stimulating glucose output at concentrations as low as 0.15 microM, with half-maximal stimulation at approx. 1 microM, and ATP was slightly less potent, half-maximal stimulation requiring 4 microM-ATP. AMP and adenosine were much less effective, doses giving half-maximal stimulation being 40 and 20 microM respectively. Non-hydrolysed ATP analogues were much less effective than ATP in promoting changes in hepatic metabolism. ITP, GTP and GDP caused similar changes in hepatic metabolism to ATP, but were 10-20 times less potent than ATP. In livers perfused at low (7 microM) Ca2+, infusion of phenylephrine before ATP desensitized hepatic responses to ATP. Repeated infusions of ATP in such low-Ca2+-perfused livers caused homologous desensitization of ATP responses, and also desensitized subsequent Ca2+-dependent responses to phenylephrine. A short infusion of Ca2+ (1.25 mM) after phenylephrine infusion restored subsequent responses to ATP, indicating that, during perfusion with buffer containing 7 microM-Ca2+, ATP and phenylephrine deplete the same pool of intracellular Ca2+, which can be rapidly replenished in the presence of extracellular Ca2+. Measurement of cyclic AMP in freeze-clamped liver tissue demonstrated that adenosine (150 microM) significantly increased hepatic cyclic AMP, whereas ATP (15 microM) was without effect. It is concluded that ATP and ADP stimulate hepatic glycogenolysis via P2-purinergic receptors, through a Ca2+-dependent mechanism similar to that in alpha-adrenergic stimulation of hepatic tissue. However, adenosine stimulates glycogenolysis via P1-purinoreceptors and/or uptake into the cell, at least partially through a mechanism involving increase in cyclic AMP. Further, the hepatic response to adenine nucleotides may be significant in regulating hepatic glucose output in physiological and pathophysiological states.

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“…I then moved on to the portal vein, which, at that time, in the rabbit was the best example of purinergic inhibitory neurotransmission outside of the gastrointestinal tract [19,20]. These experiments did produce two papers on the modulatory actions of purines on sympathetic neurotransmission [21,22], but they did not meet the challenge of being interesting.…”

Section: P2 Receptor Subtypesmentioning

confidence: 99%