PMID- 16287463
OWN - NLM
STAT- MEDLINE
DCOM- 20051223
LR  - 20131121
IS  - 1464-4096 (Print)
IS  - 1464-4096 (Linking)
VI  - 96
IP  - 9
DP  - 2005 Dec
TI  - ATP- and adenosine-induced relaxation of the smooth muscle of the pig urethra.
PG  - 1386-91
AB  - OBJECTIVES: To investigate relaxation mechanisms for ATP and adenosine in the pig 
      urethra, together with the possible role of ATP in nerve-evoked urethral 
      relaxations, as ATP is thought to cause bladder smooth muscle contraction via P2X 
      receptors, whereas relaxation is mediated via G-protein coupled P2Y receptors, 
      and ATP may also induce relaxation via breakdown to adenosine. MATERIALS AND 
      METHODS: Circular muscle strips from the female pig urethra were mounted in 
      tissue baths to record force; the effects of increasing concentrations of 1-300 
      microM ATP, the P2-receptor agonist 2-methylthioATP (2-MeSATP), adenosine, the 
      stable adenosine-analogue, 5'(N-ethylcarboxamido) adenosine (NECA), ADP, 
      uridine-triphosphate (UTP) and alpha,beta-methylene-ATP were assessed on the 
      spontaneously developed tone. Responses to ATP were further assessed in the 
      presence of G-protein activator guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS; 
      1-10 microM), the G-protein inhibitor guanosine 5'-O-(2-thio-diphosphate) 
      (GDPbetaS; 10-100 microM), suramin (1-100 microM), the ecto-ATPase inhibitor 
      6-N,N-diethyl-beta-gamma-dibromomethylene-D-adenosine-5-triphosphate (ARL 67156, 
      10-100 microM), and the suggested P2Y receptor antagonist, reactive blue-2 (1-100 
      microM). The effect of the adenosine (P1) receptor antagonist 
      8-(p-sulphophenyl)theophylline (8-SPT, 1-100 microM) on responses to adenosine, 
      and the effects of the adenosine reuptake inhibitor 
      S(p-nitrobenzyl)-6-thioinosine (NBTI, 1-100 microM) on responses to adenosine and 
      ATP were also assessed. Responses to electrical field stimulation (EFS, 12 and 30 
      Hz) in the presence of phentolamine (1 microM), scopolamine (1 microM) and N 
      omega-nitro-L-arginine (0.3 mM) were studied before and after treatment with 
      GTPgammaS, GDPbetaS, suramin, reactive blue-2 and ARL 67156. RESULTS: Strips were 
      relaxed in a concentration-dependent manner by exogenously administered ATP and 
      2-meSATP, the relaxations being slowly developing and long-lasting. The relaxant 
      effect evoked by both agonists at 300 microM amounted to about half of the 
      spontaneously developed tone. The relaxation evoked by ATP was not significantly 
      affected by GTPgammaS, GDPbetaS, suramin, ARL 67156 or reactive blue-2. Adenosine 
      induced a concentration-dependent relaxation of the smooth muscle tone, reaching 
      a maximum of approximately 70% at 300 microM, whereas 300 microM NECA only 
      relaxed the preparations by approximately 35%. The adenosine-induced relaxation 
      was not affected by treatment with 8-SPT. However, NBTI (1 microM) significantly 
      reduced the relaxation evoked by 300 microM adenosine. ADP relaxed the smooth 
      muscle tone by approximately 40% (300 microM). There was no response to UTP, and 
      the effect of alpha,beta-methylene-ATP was negligible (5% relaxation at 100 
      microM). EFS caused slowly developing and long-lasting relaxations that were 
      unaffected by GTPgammaS, GDPbetaS, suramin, reactive blue-2 and ARL 67156. 
      CONCLUSIONS: These results suggest that exogenous ATP and adenosine relax the 
      smooth muscle of the pig urethra in a manner similar to that evoked by electrical 
      stimulation of nerves, although there was no evidence for involvement of a 
      definable P2Y receptor subtype in these relaxations.
FAU - Werkstrom, Viktoria
AU  - Werkstrom V
AD  - Department of Clinical and Experimental Pharmacology, Lund University Hospital, 
      Lund, Sweden. Viktoria.Werkstrom@med.lu.se
FAU - Andersson, Karl-Erik
AU  - Andersson KE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Thionucleotides)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 71376-97-1 (guanosine 5'-O-(2-thiodiphosphate))
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*pharmacology
MH  - Adenosine Triphosphate/*pharmacology
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
MH  - Guanosine Diphosphate/analogs & derivatives/pharmacology
MH  - Muscle Relaxation/*drug effects/physiology
MH  - Muscle, Smooth/*drug effects
MH  - Swine
MH  - Thionucleotides/pharmacology
MH  - Urethra/*drug effects
EDAT- 2005/11/17 09:00
MHDA- 2005/12/24 09:00
CRDT- 2005/11/17 09:00
PHST- 2005/11/17 09:00 [pubmed]
PHST- 2005/12/24 09:00 [medline]
PHST- 2005/11/17 09:00 [entrez]
AID - BJU5853 [pii]
AID - 10.1111/j.1464-410X.2005.05853.x [doi]
PST - ppublish
SO  - BJU Int. 2005 Dec;96(9):1386-91. doi: 10.1111/j.1464-410X.2005.05853.x.