Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non‐adrenergic inhibitory nerves in the gut

Burnstock, Geoffrey; Campbell, G.; Satchell, D.G.; Smythe, A.

doi:10.1111/j.1476-5381.1970.tb10646.x

Cited by 652 publications

(322 citation statements)

References 47 publications

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“…Recently, 3', 5'-cyclic adenosine monophosphate (3', 5'-cyclic AMP) is being discussed as the second messenger in the beta-adrenergic action (1) and adenosine triphosphate (ATP) as the inhibitory transmitter of the unknown nerves in the stomach (2). To date, these actions on the cholinergic nerves in the ileum are not yet clear.…”

mentioning

confidence: 99%

Effect of N6, 2'-O-Dibutyryl 3'5'-Cyclic Adenosine Monophosphate, 3', 5', -Cyclic Adenosine Monophosphate and Adenosine Triphosphate on Acetylcholine Output From Cholinergic Nerves in Guinea Pig Ileum

Takagi

Takayanagi

1972

Jpn.J.Pharmacol

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mentioning

confidence: 99%

Effect of N6, 2'-O-Dibutyryl 3'5'-Cyclic Adenosine Monophosphate, 3', 5', -Cyclic Adenosine Monophosphate and Adenosine Triphosphate on Acetylcholine Output From Cholinergic Nerves in Guinea Pig Ileum

Takagi

Takayanagi

1972

Jpn.J.Pharmacol

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“…The transmitters responsible for inhibitory neurotransmission have been the subject of studies for several decades, and several substances have been proposed as cotransmitters mediating the postjunctional effects of inhibitory neurotransmission. ATP has been a candidate inhibitory (also called a nonadrenergic, noncholinergic) neurotransmitter in visceral muscles for many years (2,3). However, the identity of ATP as an inhibitory transmitter remains controversial (4,5), and many investigators continue to refer to the actual transmitter substance as a purine or purine-like substance.…”

mentioning

confidence: 99%

β-Nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle

Mutafova‐Yambolieva

Hwang

Hao

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

164

325

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Peripheral inhibitory nerves are physiological regulators of the contractile behavior of visceral smooth muscles. One of the transmitters responsible for inhibitory neurotransmission has been reputed to be a purine, possibly ATP. However, the exact identity of this substance has never been verified. Here we show that ␤-nicotinamide adenine dinucleotide (␤-NAD), an inhibitory neurotransmitter candidate, is released by stimulation of enteric nerves in gastrointestinal muscles, and the pharmacological profile of ␤-NAD mimics the endogenous neurotransmitter better than ATP. Levels of ␤-NAD in superfusates of muscles after nerve stimulation exceed ATP by at least 30-fold; unlike ATP, the release of ␤-NAD depends on the frequency of nerve stimulation. ␤-NAD is released from enteric neurons, and release was blocked by tetrodotoxin or -conotoxin GVIA. ␤-NAD is an agonist for P2Y1 receptors, as demonstrated by receptor-mediated responses in HEK293 cells expressing P2Y1 receptors. Exogenous ␤-NAD mimics the effects of the enteric inhibitory neurotransmitter. Responses to ␤-NAD and inhibitory junction potentials are blocked by the P2Y1-selective antagonist, MRS2179, and the nonselective P2 receptor antagonists, pyridoxal phosphate 6-azophenyl-2,4-disulfonic acid and suramin. Responses to ATP are not blocked by these P2Y receptor inhibitors. The expression of CD38 in gastrointestinal muscles, and specifically in interstitial cells of Cajal, provides a means of transmitter disposal after stimulation. ␤-NAD meets the traditional criteria for a neurotransmitter that contributes to enteric inhibitory regulation of visceral smooth muscles.enteric nervous system ͉ gastrointestinal motility ͉ P2Y receptor ͉ purinergic neurotransmission ͉ interstitial cells of Cajal

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“…At that time the result was very controversial since it was not easy to accept that the main energy molecule produced in the mitochondria it was also a chemical neurotransmitter. At present we know that ATP is released by inhibitory neurons and relaxes smooth muscle, and "purinergic" neurons have been identified with the quinacrine technique (27,28). This technique labels vesicles with high ATP contents, which probably does not guarantee their being exclusively purinergic.…”

Section: Early Studiesmentioning

confidence: 99%

Mechanisms responsible for neuromuscular relaxation in the gastrointestinal tract

Gallego¹,

Mañé²,

Gil³

et al. 2016

Rev Esp Enferm Dig

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The enteric nervous system (ENS) is responsible for the genesis of motor patterns ensuring an appropriate intestinal transit. Enteric motor neurons are classified into afferent neurons, interneurons and motorneurons. Motorneurons are excitatory or inhibitory causing smooth muscle contraction and relaxation respectively. Muscle relaxation mechanisms are key for the understanding of physiological processes such as sphincter relaxation, gastric accommodation, or the descending phase of the peristaltic reflex. Nitric oxide (NO) and ATP or a related purine are the primary inhibitory neurotransmitters. Nitrergic neurons synthesize NO through nNOS enzyme activity. NO diffuses across the cell membrane to bind guanylyl cyclase, and then activates a number of intracellular mechanisms that ultimately result in muscle relaxation. ATP is an inhibitory neurotransmitter together with NO. The P2Y1 receptor has been identified as a the purine receptor responsible for smooth muscle relaxation. Although, probably, no clinician doubts about the significance of NO in the pathophysiology of gastrointestinal motility, the relevance of purinergic neurotransmission is apparently much lower, as ATP has not been associated with any specific motor dysfunction yet. The goal of this review is to discuss the function of both relaxation mechanisms in order to establish the physiological grounds of potential motor dysfunctions arising from impaired intestinal relaxation.

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Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non‐adrenergic inhibitory nerves in the gut

Cited by 652 publications

References 47 publications

Effect of N6, 2'-O-Dibutyryl 3'5'-Cyclic Adenosine Monophosphate, 3', 5', -Cyclic Adenosine Monophosphate and Adenosine Triphosphate on Acetylcholine Output From Cholinergic Nerves in Guinea Pig Ileum

Effect of N6, 2'-O-Dibutyryl 3'5'-Cyclic Adenosine Monophosphate, 3', 5', -Cyclic Adenosine Monophosphate and Adenosine Triphosphate on Acetylcholine Output From Cholinergic Nerves in Guinea Pig Ileum

β-Nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle

Mechanisms responsible for neuromuscular relaxation in the gastrointestinal tract

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