Identification of Separate Receptors for Adenosine and Adenosine 5′‐triphosphate in Causing Relaxations of the Isolated Taenia of the Guinea‐pig Caecum

Spedding, Michael; Weetman, D.F.

doi:10.1111/j.1476-5381.1976.tb07480.x

Cited by 49 publications

(25 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After an early hint (Spedding and Weetman, 1976), receptors for purines were subdivided into P1 (adenosine) and P2 (ATP and ADP) receptors (Burnstock, 1978), and later subdivision of P2 receptors into P2X and P2Y subtypes was made on the basis of pharmacology (Burnstock and Kennedy, 1985). It was recognized that some P2Y receptors responded to pyrimidines as well as purines (Seifert and Schultz, 1989).…”

Section: Brief Historical Background Of Nucleotides and Their Recementioning

confidence: 99%

International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy

Abbracchio

Burnstock

Boeynaems

et al. 2006

Pharmacological Reviews

1,148

1,346

View full text Add to dashboard Cite

Section: Brief Historical Background Of Nucleotides and Their Recementioning

confidence: 99%

International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy

Abbracchio

Burnstock

Boeynaems

et al. 2006

Pharmacological Reviews

1,148

1,346

View full text Add to dashboard Cite

“…However, PIT does not antagonize the relaxant effects of adenosine (Spedding & Weetman, 1976), nor are the relaxant effects of non-adrenergic inhibitory nerves antagonized (Spedding, Sweetman & Weetman, 1975). From this latter evidence it is unlikely that the inhibitory neurotransmitter is ATP.…”

Section: Introductionmentioning

confidence: 87%

The Mechanism of the Relaxant Effect of 2‐2′‐pyridylisatogen on the Isolated Taenia of the Guinea‐pig Caecum

Spedding

Weetman

1978

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 2-2'-Pyridylisatogen tosylate (PIT) slowly relaxed taenia caeci preparations of the guinea-pig in a concentration-dependent manner (threshold 2.5 giM). The relaxant effect did not show tachyphylaxis.2 The relaxation was not affected by tetrodotoxin (0.3 gM), guanethidine (17 jM) nor by a combination of phentolamine (36 gM) and propranolol (4 gM) 3 In taenia caeci preparations suspended in K+-depolarizing, Ca2+-free Ringer, addition of Ca2+ (0.1 to 30 mM) resulted in a slow contraction. PIT (50 gM) and papaverine (15 jM) antagonized these contractions, whereas indomethacin (28 jM) was ineffective. 4 Although PIT (50 M for 30 min) caused a relaxation of the taenia, and, when the tone of the preparations was restored with carbachol, antagonized adenosine 5'-triphosphate (ATP)-induced relaxations, relaxation of the taenia with papaverine (30 gM for 5 min) did not antagonize ATPinduced relaxations. It is concluded that the relaxant and ATP-receptor blocking actions of PIT are independent properties of the compound.

show abstract

“…PIT had been used to differentiate P1 (adenosine) and P2 (nucleotide) receptors [8]. It was later demonstrated that PIT is an allosteric modulator of the chicken P2Y 1 receptor expressed in Xenopus oocytes [9].…”

Section: Introductionmentioning

confidence: 99%

2,2′-Pyridylisatogen tosylate antagonizes P2Y1 receptor signaling without affecting nucleotide binding

Gao¹,

Mamedova²,

Tchilibon³

et al. 2004

Biochemical Pharmacology

View full text Add to dashboard Cite

The effect of 2,2′-pyridylisatogen tosylate (PIT) on the human P2Y 1 receptor and on other recombinant P2Y receptors has been studied. We first examined the modulation by PIT of the agonist-induced accumulation of inositol phosphates. PIT blocked 2-methylthio-ADP (2-MeSADP)-induced accumulation of inositol phosphates in 1321N1 astrocytoma cells stably expressing human P2Y 1 receptors in a non-competitive and concentration-dependent manner. The IC 50 for reduction of the maximal agonist effect was 0.14 μM. In contrast, MRS2179, a competitive P2Y 1 receptor antagonist, parallel-shifted the agonist concentration-response curve to the right. PIT also concentration-dependently blocked the P2Y 1 receptor signaling induced by the endogenous agonists, ADP and ATP. A simple structural analogue of PIT was synthesized and found to be inactive as a P2Y 1 receptor antagonist, suggesting that the nitroxyl group of PIT is a necessary structural component for P2Y 1 receptor antagonism. We next examined the possible modulation of the binding of the newly available antagonist radioligand for the P2Y 1 receptor, [ 3 H] MRS2279. It was found that PIT (0.01-10 μM) did not inhibit [ 3 H] MRS2279 binding to the human P2Y 1 receptor. PIT (10 μM) had no effect on the competition for [ 3 H] MRS2279 binding by agonists, ADP and ATP, suggesting that its antagonism of the P2Y 1 receptor may be allosteric. PIT had no significant effect on agonist activation of other P2Y receptors, including P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 and P2Y 12 receptors. Thus, PIT selectively and non-competitively blocked P2Y 1 receptor signaling without affecting nucleotide binding.

show abstract

Identification of Separate Receptors for Adenosine and Adenosine 5′‐triphosphate in Causing Relaxations of the Isolated Taenia of the Guinea‐pig Caecum

Cited by 49 publications

References 10 publications

International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy

International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy

The Mechanism of the Relaxant Effect of 2‐2′‐pyridylisatogen on the Isolated Taenia of the Guinea‐pig Caecum

2,2′-Pyridylisatogen tosylate antagonizes P2Y1 receptor signaling without affecting nucleotide binding

Contact Info

Product

Resources

About