PMID- 8591002
OWN - NLM
STAT- MEDLINE
DCOM- 19960404
LR  - 20190512
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 116
IP  - 6
DP  - 1995 Nov
TI  - Structure-activity relationship of a pyrimidine receptor in the rat isolated 
      superior cervical ganglion.
PG  - 2764-70
AB  - 1. The effects of pyrimidines and purines on the d.c. potential of the rat 
      isolated superior cervical ganglion (SCG) have been examined by a grease-gap 
      technique to determine the structure-activity requirements of the receptor 
      activated by pyrimidines, i.e. a pyrimidinoceptor. 2. 
      5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl (ZTP), the pyrimidines, 
      cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP) and thymidine 
      5'-triphosphate (TTP) and the purines, adenosine 5'-triphosphate (ATP; in the 
      presence of an A1-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine 
      (DPCPX) (1 microM)), adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), guanosine 
      5'-triphosphate (GTP), inosine 5'-triphosphate (1TP) depolarized ganglia in a 
      concentration-dependent manner. The relative order of ZTP and purine 
      5'-triphosphates in depolarizing ganglia was ZTP > or = ATP gamma S > > ATP > or 
      = ITP = GTP, and for the pyrimidine 5'-triphosphates UTP > TTP > or = CTP. 
      Depolarizations evoked by ATP gamma S were followed by concentration-dependent 
      hyperpolarizations at 100 and 1000 microM. 3. At concentrations of between 0.1 
      microM and 1 mM, uridine 5'-diphosphate (UDP), uridine 5'-diphosphoglucose (UDPG) 
      and uridine 5'-diphosphoglucuronic acid (UDPGA) evoked significant and 
      concentration-dependent depolarizations, whereas uridine 5'-monophosphate (UMP), 
      uridine and uracil were inactive or produced small (< 45 microV) depolarizations. 
      The relative order of potency of uridine analogues in depolarizing ganglia was 
      UDP > or = UTP > UDPG > UDPGA > > uracil > or = UMP = pseudouridine > or = 
      uridine. At 3 and 10 mM, uridine produced concentration-dependent 
      hyperpolarizations. Nikkomycin Z, a nucleoside resembling UTP (viz. the 
      triphosphate chain at the 5'-position on the ribose moiety being replaced by a 
      peptide), was inactive between 1 microM and 1 mM. Generally, a concentration of 
      10 mM was required before thymidine, 6-azathymine, 6-azauracil or 6-azauridine 
      depolarized ganglia. 4. Suramin (300 microM), a P2-purinoceptor antagonist, 
      significantly depressed depolarizations evoked by alpha, beta-methylene-ATP 
      (alpha, beta-MeATP; 100 microM), ATP gamma S (100 microM), CTP (1 mM), GTP (1 
      mM), ZTP (30 microM) and ATP (300 microM) in the presence of DPCPX (1 microM). 
      Suramin reversed a small depolarization evoked by UMP (1 mM) into a small 
      hyperpolarization. In contrast depolarizations evoked by UDP, UTP, UDPG (all at 
      100 microM) and TTP (300 microM) were unaltered or enhanced by suramin. 5. It is 
      concluded that the rat SCG contains distinct nucleotide receptors including a 
      P2-purinoceptor (activated by alpha, beta-MeATP, ATP, GTP, ITP and ZTP) and a 
      pyrimidinoceptor (activated by UTP, UDP, UDPG, UDPGA and TTP). The 
      pyrimidinoceptor on rat SCG neurones had specific structure activity requirements 
      with the di- and triphosphates of uridine being the most effective depolarizing 
      agonists examined.
FAU - Connolly, G P
AU  - Connolly GP
AD  - Department of Physiology, University College London.
FAU - Harrison, P J
AU  - Harrison PJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Aminoglycosides)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Pyrimidine Nucleosides)
RN  - 0 (Pyrimidine Nucleotides)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 6032D45BEM (Suramin)
RN  - 82989-82-0 (5-aminoimidazole-4-carboxamide-1-ribofuranosyl triphosphate)
RN  - 9Z22C3QQCJ (nikkomycin)
RN  - UT0S826Z60 (Uridine Triphosphate)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
MH  - *Aminoglycosides
MH  - Aminoimidazole Carboxamide/pharmacology
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Male
MH  - Membrane Potentials/drug effects
MH  - Pyrimidine Nucleosides/metabolism/pharmacology
MH  - Pyrimidine Nucleotides/metabolism/pharmacology
MH  - Pyrimidines/metabolism/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cell Surface/*drug effects/*physiology
MH  - Ribonucleotides/pharmacology
MH  - Structure-Activity Relationship
MH  - Superior Cervical Ganglion/drug effects/*ultrastructure
MH  - Suramin/pharmacology
MH  - Uridine/analogs & derivatives/pharmacology
MH  - Uridine Triphosphate/pharmacology
PMC - PMC1909137
EDAT- 1995/11/01 00:00
MHDA- 1995/11/01 00:01
PMCR- 1996/11/01
CRDT- 1995/11/01 00:00
PHST- 1995/11/01 00:00 [pubmed]
PHST- 1995/11/01 00:01 [medline]
PHST- 1995/11/01 00:00 [entrez]
PHST- 1996/11/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1995.tb17239.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1995 Nov;116(6):2764-70. doi: 10.1111/j.1476-5381.1995.tb17239.x.