Adenosine 5'-triphosphate and noradrenaline are excitatory cotransmitters to the fibromuscular stroma of the guinea pig prostate gland

Eur J Pharmacol. 2004 Sep 24;499(3):335-44. doi: 10.1016/j.ejphar.2004.07.080.

Abstract

Immunohistochemical studies demonstrated abundant P2X(1)-receptor immunoreactivity colocalized with alpha-actin within the fibromuscular stroma of the guinea pig prostate. P2X(2)-, P2X(3)- and P2X(4)-receptor immunoreactivity was absent. alphabetamethylene Adenosine 5'-triphosphate (ATP) attenuated contractile responses to electrical field stimulation (50 V, 0.5 ms, 5-20 Hz) in the absence and presence of prazosin (0.3 microM). Responses to 1-2 Hz were unaffected. ARL 67156 (6-N, N-diethyl-beta-gamma-dibromomethylene-D-adenosine-5-triphosphate; 100 microM) enhanced contractile responses to electrical field stimulation (50 V, 0.5 ms, 10-20 Hz). Concentration-response curves to exogenously applied ATP analogues on unstimulated preparations elicited concentration-dependent suramin (100 microM)-sensitive contractions. The rank order of potency was: alphabetamethylene ATP>2methylthio ATP=betagammamethylene ATP>adenosine 5'-diphosphate (ADP)=ATP. Adenosine and adenosine 5'-monophosphate (AMP) did not produce contractile responses. These results demonstrate the presence of functional P2X(1)-receptors within the fibromuscular stroma of the guinea pig prostate and suggest a cotransmitter role for ATP with noradrenaline during high-frequency stimulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology*
  • Adenosine Triphosphate / physiology
  • Animals
  • Atropine / pharmacology
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Guinea Pigs
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology
  • Norepinephrine / metabolism
  • Norepinephrine / physiology*
  • Prazosin / pharmacology
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / physiology
  • Receptors, Purinergic P2 / analysis
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2X2
  • Receptors, Purinergic P2X4
  • Suramin / pharmacology
  • Tetrodotoxin / pharmacology
  • Thionucleotides / pharmacology

Substances

  • 6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP
  • Actins
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2X2
  • Receptors, Purinergic P2X4
  • Thionucleotides
  • Tetrodotoxin
  • Suramin
  • Adenosine Diphosphate
  • Atropine
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • alpha,beta-methyleneadenosine 5'-triphosphate
  • Norepinephrine
  • Prazosin
  • 2-methylthio-ATP