Effector mechanisms for α,β-methylene ATP and ATP derivatives in guinea-pig taenia caeci

Hertog, Adriaan den; Pielkenrood, Jacqueline; Akker, Jan van den

doi:10.1016/0014-2999(85)90033-0

Cited by 22 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We suggest that they could both represent different types of the P2Y receptors family. The data supporting this suggestion are as follows: (i) the hyperpolarization evoked by ATP, α,β‐meATP and ADPβS in the intestinal smooth muscle is due to the mobilization of intracellular Ca 2+ and the secondary activation of Ca 2+ ‐dependent K + channels (Den Hertog et al , 1985; Zagorodnyuk & Shuba, 1986; Zagorodnyuk et al , 1989; present study); (ii) the latency of the apamin‐sensitive NANC i.j.p. which has an ionic mechanism similar to that of the ATP‐and α,β‐meATP‐mediated hyperpolarization, is about 10 fold longer than that of the P2X receptor‐mediated NANC e.j.p.…”

Section: Discussionsupporting

confidence: 70%

“…in guinea‐pig colon can hardly be explained with the involvement of a ligand gated ion channel (Zagorodnyuk et al , 1996); (b) the mobilization of intracellular Ca 2+ and secondary activation of Ca 2+ ‐dependent K + conductance is responsible for the P2 receptor‐activated hyperpolarization and for the genesis of the apamin‐sensitive NANC i.j.p. (Den Hertog et al , 1985; Zagorodnyuk & Shuba, 1986; Zagorodnyuk et al , 1989), a chain of events more consistent with the involvement of a metabotropic receptor rather than of a ligand‐gated cation channel.…”

Section: Introductionmentioning

confidence: 89%

See 1 more Smart Citation

Pharmacological evidence for the existence of multiple P2 receptors in the circular muscle of guinea‐pig colon

Zagorodnyuk

Maggi

1998

British J Pharmacology

View full text Add to dashboard Cite

1 By using the sucrose gap technique, we have investigated the e ect of the metabolically stable P2Y receptor agonist, adenosine 5'-O-2-thiodiphosphate (ADPbS), on the membrane potential and tension in the circular muscle of the guinea-pig proximal colon. All experiments were performed in the presence of atropine (1 mM), guanethidine (3 mM), indomethacin (3 mM), nifedipine (1 mM), L-nitroarginine (L-NOARG, 100 mM) and of the tachykinin NK 1 and NK 2 receptor antagonists, SR 140333 (0.1 mM) and GR 94800 (0.1 mM), respectively. 2 ADPbS (100 mM for 15 s) evoked a tetrodotoxin-(1 mM) resistant hyperpolarization and contraction of the smooth muscle. In the presence of apamin (0.1 mM), the ADPbS-induced hyperpolarization was converted to depolarization and the contraction was potentiated while tetraethylammonium (TEA, 10 mM) did not a ect signi®cantly the response to ADPbS. The combined application of apamin and TEA reproduced the e ect observed with apamin alone. 3 Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acids (PPADS, 30 mM) slightly but signi®cantly increased the ADPbS-induced hyperpolarization, while the contraction evoked by ADPbS was reduced by about 80%. Suramin (100 mM) did not a ect the ADPbS-induced hyperpolarization but totally blocked the ADPbS-induced contraction. In the presence of suramin (100 mM), a small relaxation of the circular muscle was observed upon application of ADPbS. 4 The contraction and hyperpolarization evoked by ADPbS were abolished in Ca 2+ -free Krebs solution. The blocker of sarcoplasmic reticulum Ca 2+ pump, cyclopiazonic acid (10 mM) reduced contraction and hyperpolarization induced by ADPbS by about 60 and 50%, respectively. 5 A comparison of our present and previous ®ndings enables to conclude that at least 3 types of P2 receptors are present on the smooth muscle of the guinea-pig colon, as follows: (1) inhibitory P2 receptors, producing an apamin-sensitive hyperpolarization, which are activated by a,b-methylene ATP (a,b-meATP) and by endogenously released purines, sensitive to suramin and PPADS; (2) inhibitory P2 receptors, producing an apamin-sensitive hyperpolarization, which are activated by ADPbS and are resistant to suramin and PPADS; (3) excitatory P2 receptors, producing contraction, which are activated by ADPbS and are sensitive to suramin and PPADS. The data also support the idea of the existence of a restricted pool of specialized junctional P2 receptors producing the apamin-sensitive NANC inhibitory junction potential in response to endogenous ligand(s).

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 89%

Pharmacological evidence for the existence of multiple P2 receptors in the circular muscle of guinea‐pig colon

Zagorodnyuk

Maggi

1998

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…In hindsight, it is also unremarkable to link ␣␤meATP-evoked relaxations with P2Y 11 activation, because an extended series of methylene phosphonate derivatives (␤␥meATP, ␤␥Cl 2 meATP, and 2-methylthio-␤␥Cl 2 meATP), which are structurally related to the P2Y 11 agonist ARC67085 are also highly potent relaxants of the taenia (Cusack et al, 1987). Furthermore, ␣␤meATP can directly open apamin sensitive K ϩ channels in the taenia, even in the absence of extracellular calcium, by stimulating a suramin-sensitive P2Y receptor that mobiles intracellular Ca 2ϩ stores (Den Hertog et al, 1985). We confirmed that suramin can antagonize Ca 2ϩ responses mediated by BzATP-stimulated human P2Y 11 receptors, and we also showed that Reactive Red can do the same.…”

Section: Discussionmentioning

confidence: 99%

Involvement of P2Y₁and P2Y₁₁Purinoceptors in Parasympathetic Inhibition of Colonic Smooth Muscle

King

Townsend‐Nicholson²

2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Purinergic signaling was first recognized in the guinea pig (Cavia porcellus) taenia coli, where relaxation of smooth muscle by nerve-released ATP may involve the activation of P2Y 1 and P2Y 11 receptors, and where transcripts for both genes have been found. A partial sequence for P2Y 11 protein was identified; the full-length P2Y 1 sequence has already been described. P2Y 1 and P2Y 11 proteins were localized by immunohistochemistry in smooth muscle cells. P2X 2 and P2X 3 proteins were also localized in motoneurons of the myenteric plexus. ␣␤-Methylene-ATP (␣␤meATP) and dibenzoyl-ATP (BzATP) evoked fast relaxations in the taenia, and they were inhibited by the P2Y 1 receptor antagonist 2Ј-deoxy-N 6 -methyladenosine 3Ј,5Ј-bisphosphate (MRS2179). However, ␣␤meATP and BzATP may stimulate neuronal P2X receptors to release ATP, which then acts on P2Y 1 receptors. In accordance, fast relaxations evoked by ␣␤meATP and BzATP were inhibited by the P2X 3 and P2X 2/3 receptor antagonist 5-({[3-phenoxybenzyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl] amino} carbonyl)-1,2,4-benzene-tricarboxylic acid (A317491). When P2Y 1 , P2X 3 , and P2X 2/3 receptors were blocked and adenosine was removed enzymatically, ␣␤meATP and BzATP evoked slow relaxations that were inhibited by Reactive Red. Fast and slow relaxations involve small and large conductance calcium-activated potassium channels; the latter are dependent on intracellular cyclic AMP levels, which altered the duration and amplitude of relaxations. ␣␤meATP and BzATP were confirmed as agonists, and Reactive Red as an antagonist, of human P2Y 11 receptors. In summary, G q -coupled P2Y 1 receptors are involved mainly in fast relaxations, whereas G qand G s -coupled P2Y 11 receptors are involved in both fast and slow relaxations. These P2Y receptor subtypes, plus neuronal P2X receptors, may explain the phenomenon of parasympathetic inhibition first described by Langley (1898).

show abstract

“…Consequently, addition of ATP may stimu late both ATP-sensitive and adenosine-sensi tive receptors. Adenosine caused a sustained hyperpolarization which is more pronounced in Krebs than in calcium-free solution [Den Hertog et al, 1985]. This hyperpolarization is thought to be due to stimulation of calcium extrusion [Frischknecht and Ferrero, 1984], a mechanism possibly also involved in the ac tion of isoprénaline [Biilbring and Den Her tog, 1980;this paper].…”

Section: Discussionmentioning

confidence: 99%

Some Effects of Orthovanadate on Smooth Muscle Cells of Guinea-Pig Taenia caeci

Hertog¹,

Pielkenrood²,

Akker³

1985

Pharmacology

Self Cite

View full text Add to dashboard Cite

The effect of orthovanadate on the response caused by the β-adrenergic receptor agonist isoprenaline and on the ATP response were investigated by measuring potential changes and changes in the contractile state of smooth muscle cells of guinea-pig taenia caeci at 35 °C using the sucrose-gap method. The contraction evoked by carbachol (10^–7M) or potassium (15 mM) was not modified by orthovanadate (1.0 mM). The hyperpolarization evoked in smooth muscle cells by ATP (0.4 mM) was affected to some extent by orthovanadate (1.0 mM), but was not modified in the absence of extracellular calcium. The hyperpolarization caused by isoprenaline (3 × 10^–6M), however, was inhibited completely both in the presence and absence of calcium. These results are consistent with the view that isoprenaline activates calcium extrusion from the smooth muscle cells, a process being electrogenic in nature.

show abstract

Effector mechanisms for α,β-methylene ATP and ATP derivatives in guinea-pig taenia caeci

Cited by 22 publications

References 13 publications

Pharmacological evidence for the existence of multiple P2 receptors in the circular muscle of guinea‐pig colon

Pharmacological evidence for the existence of multiple P2 receptors in the circular muscle of guinea‐pig colon

Involvement of P2Y₁and P2Y₁₁Purinoceptors in Parasympathetic Inhibition of Colonic Smooth Muscle

Some Effects of Orthovanadate on Smooth Muscle Cells of Guinea-Pig Taenia caeci

Contact Info

Product

Resources

About

Effector mechanisms for α,β-methylene ATP and ATP derivatives in guinea-pig taenia caeci

Cited by 22 publications

References 13 publications

Pharmacological evidence for the existence of multiple P2 receptors in the circular muscle of guinea‐pig colon

Pharmacological evidence for the existence of multiple P2 receptors in the circular muscle of guinea‐pig colon

Involvement of P2Y1and P2Y11Purinoceptors in Parasympathetic Inhibition of Colonic Smooth Muscle

Some Effects of Orthovanadate on Smooth Muscle Cells of Guinea-Pig Taenia caeci

Contact Info

Product

Resources

About

Involvement of P2Y₁and P2Y₁₁Purinoceptors in Parasympathetic Inhibition of Colonic Smooth Muscle