PMID- 10638758
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20101118
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 403
IP  - 6765
DP  - 2000 Jan 6
TI  - Reduced vas deferens contraction and male infertility in mice lacking P2X1
      receptors.
PG  - 86-9
AB  - P2X1 receptors for ATP are ligand-gated cation channels, present on many
      excitable cells including vas deferens smooth muscle cells. A substantial
      component of the contractile response of the vas deferens to sympathetic nerve
      stimulation, which propels sperm into the ejaculate, is mediated through P2X
      receptors. Here we show that male fertility is reduced by approximately 90% in
      mice with a targeted deletion of the P2X1 receptor gene. Male mice copulate
      normally--reduced fertility results from a reduction of sperm in the ejaculate
      and not from sperm dysfunction. Female mice and heterozygote mice are unaffected.
      In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic
      nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists 
      are abolished. These results show that P2X1 receptors are essential for normal
      male reproductive function and suggest that the development of selective P2X1
      receptor antagonists may provide an effective non-hormonal male contraceptive
      pill. Also, agents that potentiate the actions of ATP at P2X1 receptors may be
      useful in the treatment of male infertility.
FAU - Mulryan, K
AU  - Mulryan K
AD  - Department of Cell Physiology & Pharmacology, University of Leicester, UK.
FAU - Gitterman, D P
AU  - Gitterman DP
FAU - Lewis, C J
AU  - Lewis CJ
FAU - Vial, C
AU  - Vial C
FAU - Leckie, B J
AU  - Leckie BJ
FAU - Cobb, A L
AU  - Cobb AL
FAU - Brown, J E
AU  - Brown JE
FAU - Conley, E C
AU  - Conley EC
FAU - Buell, G
AU  - Buell G
FAU - Pritchard, C A
AU  - Pritchard CA
FAU - Evans, R J
AU  - Evans RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Purinergic P2 Receptor Agonists)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2X)
SB  - IM
CIN - Nature. 2000 Jan 6;403(6765):35. PMID: 10651565
MH  - Animals
MH  - Contraception
MH  - Ejaculation/physiology
MH  - Female
MH  - Gene Deletion
MH  - Infertility, Male/*etiology/genetics
MH  - Male
MH  - Mice
MH  - Muscle Contraction
MH  - Muscle, Smooth/physiology
MH  - Pregnancy
MH  - Purinergic P2 Receptor Agonists
MH  - Receptors, Purinergic P2/deficiency/genetics/*physiology
MH  - Receptors, Purinergic P2X
MH  - Reproduction
MH  - Sperm Count
MH  - Sympathetic Nervous System/physiology
MH  - Vas Deferens/*physiopathology
EDAT- 2000/01/19 09:00
MHDA- 2001/03/23 10:01
CRDT- 2000/01/19 09:00
PHST- 2000/01/19 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 2000/01/19 09:00 [entrez]
AID - 10.1038/47495 [doi]
PST - ppublish
SO  - Nature. 2000 Jan 6;403(6765):86-9. doi: 10.1038/47495.