Evidence from desensitization studies for distinct receptors for ATP and UTP on the rat superior cervical ganglion

Connolly, G.P.

doi:10.1111/j.1476-5381.1994.tb13079.x

Cited by 22 publications

(15 citation statements)

References 8 publications

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“…An inhibition of ectonucleotidase activity by suramin (Hourani & Chown, 1989) could also account for the ability of suramin (but not reactive blue 2, which does not inhibit ectonucleotidases, Hourani & Chown, 1989) to enhance UTP-evoked depolarizations. Apart from studies using P2-purinoceptor antagonists there is additional evidence that ATP and UTP activate distinct receptors, which is based upon desensitization studies (Connolly, 1994a). Further experiments to examine the effect of specific inhibitors of ectonucleotidases on purine and pyrimidine evoked responses of the rat SCG should help resolve these issues.…”

Section: Discussionmentioning

confidence: 99%

“…Recently it has been proposed that neurones of the rat superior cervical ganglion (SCG) possess pyrimidinoceptors and that this preparation is a model tissue for the study of pyrimidinoceptors within the nervous system (Connolly & Harrison, 1993;Connolly et al, 1993b;Connolly, 1994a). This hypothesis was based upon the observation that there are distinct receptors that are activated by UTP but not by ATP or x, methylene adenosine 5'-triphosphate (m,-Me-ATP) (a selective P2X-purinoceptor agonist (Burnstock & Kennedy, 1985)).…”

Section: Introductionmentioning

confidence: 99%

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Differentiation by pyridoxal 5‐phosphate, PPADS and IsoPPADS between responses mediated by UTP and those evoked by α,β‐methylene‐ATP on rat sympathetic ganglia

Connolly

1995

British J Pharmacology

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1 The effect of pyridoxal 5-phosphate, and the 2',4' and 2',5'-disulphonic acid isomers of 6-azophenylpyridoxal 5-phosphate (PPADS and IsoPPADS respectively) on depolarization of the rat superior cervical ganglion evoked by a,-methylene-adenosine 5'-triphosphate (a,-Me-ATP) and uridine 5'-triphosphate (UTP) were determined by a grease-gap recording technique.2 Pyridoxal 5-phosphate (10-100 tM) and PPADS (10-100 M) enhanced UTP-and depressed a,-

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differentiation by pyridoxal 5‐phosphate, PPADS and IsoPPADS between responses mediated by UTP and those evoked by α,β‐methylene‐ATP on rat sympathetic ganglia

Connolly

1995

British J Pharmacology

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“…However, cross-desensitization is seen between ATP analogues and UTP in the rat colon muscularis mucosae (P2Y) and in the mouse vas deferens (P2X) (Von Ktigelgen et al, 1990), suggesting that in some tissues UTP may act at these receptors. In addition, separate UTP receptors termed pyrimidinoceptors at which purines are not active have been proposed to exist in a number of tissues, including several blood vessels (Von Kugelgen et al, 1987;Saiag et al, 1987;1990; Kigelgen & Starke, 1990; reviewed by Seifert & Schultz, 1989), the rat superior cervical ganglion (Connolly, 1994) and C6-2B rat glioma cells (Lazarowski & Harden, 1994).…”

Section: Introductionmentioning

confidence: 99%

Responses of the longitudinal muscle and the muscularis mucosae of the rat duodenum to adenine and uracil nucleotides

Johnson

Charlton

Hourani

1996

British J Pharmacology

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1 Previous studies have shown that the rat duodenum contains PI and P2y purinoceptors via which it relaxes to adenosine and adenosine 5'-triphosphate (ATP) respectively. It has also been shown to contract to uridine 5'-triphosphate (UTP) and adenosine 5'-O-(3-thiotriphosphate) (ATP-y-S), and based on their differential inhibition by the P2 antagonist suramin it has been suggested that they act via two separate receptors. In addition, the rat duodenum has been shown to dephosphorylate ATP rapidly via ectonucleotidases and adenosine deaminase. In this study the responses of two preparations from the rat duodenum, the longitudinal muscle and the muscularis mucosae, were investigated using a series of nucleotides and suramin. 4 Suramin (1 mM) inhibited relaxations induced by ATP on the longitudinal muscle, shifting the relaxation concentration-response curve to the right. This further supports the presence of a P2Y-purinoceptor on this muscle layer. Suramin (1 mM) inhibited contractions induced by AMPCPP, but not those induced by ATP, UTP or ATP-y-S, in the muscularis mucosae. Desensitization of the muscularis mucosae was seen with AMPCPP, but not with UTP or ATP-y-S, and no cross-desensitization between AMPCPP and UTP or ATP-y-S was observed. This suggests there are two receptors which mediate contraction on the rat duodenum muscularis mucosae, one suramin-sensitive and the other suramininsensitive.5 ATP was rapidly degraded by the muscularis mucosae to ADP, adenosine 5'-monophosphate (AMP) and inosine, with no adenosine being detected. A similar rate of degradation was seen for UTP with UDP, uridine 5'-monophosphate (UMP) and uridine being formed and for 2-MeSATP with 2-methylthioadenosine 5'-diphosphate (2-MeSADP), 2-methylthioadenosine 5'-monophosphate (2-Me-SAMP) and 2-methylthioadenosine being formed. AMPCPP and ATP-y-S were both degraded more slowly, AMPCPP being degraded to AMPCP, and ATP-y-S to ADP, AMP and inosine. Suramin (1 mM), did not significantly affect the rate and pattern of degradation of these nucleotides, apart from AMPCPP which was degraded slightly more slowly in the presence of suramin. 6 These results show that there is a P2y-purinoceptor which mediates relaxation in the rat duodenum longitudinal muscle. They also show that there is a contraction-mediating suramin-sensitive receptor on the rat duodenum muscularis mucosae which is desensitized by AMPCPP, and thus is probably of the P2X subtype. In addition, there is a contraction-mediating suramin-insensitive receptor on the rat duodenum muscularis mucosae which is not desensitized by UTP or ATP-y-S, and at which ATP and UTP show equal potency, and is thus probably of the P2u subtype. In addition, the rat duodenum muscularis mucosae contains ectonucleotidases and adenosine deaminase, which rapidly degrade nucleotides, although the inhibition by suramin of this degradation is unlikely to explain the differential antagonism by suramin of the nucleotides.

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“…P2Y receptors are also expressed on sympathetic neurons (Connolly 1994;Boehm 1999Boehm , 2003Calvert et al 2004) (Fig. 7.5a).…”

Section: Sympathetic Gangliamentioning

confidence: 90%

Peripheral Nervous System

Burnstock¹,

Verkhratsky

2012

Purinergic Signalling and the Nervous System

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Evidence from desensitization studies for distinct receptors for ATP and UTP on the rat superior cervical ganglion

Cited by 22 publications

References 8 publications

Differentiation by pyridoxal 5‐phosphate, PPADS and IsoPPADS between responses mediated by UTP and those evoked by α,β‐methylene‐ATP on rat sympathetic ganglia

Differentiation by pyridoxal 5‐phosphate, PPADS and IsoPPADS between responses mediated by UTP and those evoked by α,β‐methylene‐ATP on rat sympathetic ganglia

Responses of the longitudinal muscle and the muscularis mucosae of the rat duodenum to adenine and uracil nucleotides

Peripheral Nervous System

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