PMID- 17690141
OWN - NLM
STAT- MEDLINE
DCOM- 20080117
LR  - 20240316
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 584
IP  - Pt 1
DP  - 2007 Oct 1
TI  - Blockade of phosphodiesterase Type 5 enhances rat neurohypophysial excitability 
      and electrically evoked oxytocin release.
PG  - 137-47
AB  - Phosphodiesterase type 5 (PDE5) acts specifically on cyclic guanosine 
      monophosphate (cGMP) and terminates cGMP-mediated signalling. PDE5 has a well 
      established role in vascular smooth muscle, where specific inhibitors of PDE5 
      such as sildenafil correct erectile dysfunction by augmenting cGMP-mediated 
      vascular relaxation. However, the role of PDE5 outside of the vasculature has 
      received little attention. The present study tested PDE5 inhibitors on the 
      cGMP-mediated modulation of K(+) channels in the neurohypophysis (posterior 
      pituitary). Photolysis of caged-cGMP enhanced current through Ca(2+)-activated 
      K(+) channels, and this enhancement recovered in about 2 min. Sildenafil 
      essentially eliminated this recovery, suggesting that the reversal of K(+) 
      current enhancement depends on cGMP breakdown. Activation of nitric oxide 
      synthase during trains of activity in pituitary nerve terminals enhances 
      excitability. When trains of stimulation were applied at regular intervals, 
      sildenafil enhanced the excitability of neurohypophysial nerve terminals and 
      increased the action potential firing probability. T-1032, a compound with high 
      specificity for PDE5 over PDE6, had a similar action. Voltage imaging in intact 
      neurohypophysis with a voltage sensitive absorbance dye showed that T-1032 
      reduced the failure of propagating action potentials during trains of activity. 
      This indicates that PDE5 activity limits action potential propagation in 
      neurohypophysial axons. Immunoassay of oxytocin, a neuropeptide hormone secreted 
      by the posterior pituitary, demonstrated that sildenafil increased electrically 
      evoked release. Thus, PDE5 plays an important role in the regulation of 
      neurohypophysial function, and blockade of this enzyme can enhance the 
      use-dependent facilitation of neurohypophysial secretion.
FAU - Zhang, Zhenjie
AU  - Zhang Z
AD  - Department of Physiology, University of Wisconsin, Madison WI, USA.
FAU - Klyachko, Vitaly
AU  - Klyachko V
FAU - Jackson, Meyer B
AU  - Jackson MB
LA  - eng
GR  - R01 NS030016/NS/NINDS NIH HHS/United States
GR  - R37 NS030016/NS/NINDS NIH HHS/United States
GR  - NS30016/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070809
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (Potassium Channels)
RN  - 0 (Purines)
RN  - 0 (Sulfones)
RN  - 50-56-6 (Oxytocin)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5)
SB  - IM
CIN - J Physiol. 2007 Oct 1;584(Pt 1):3. PMID: 17717007
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Cyclic Nucleotide Phosphodiesterases, Type 5/*metabolism
MH  - Electric Stimulation
MH  - In Vitro Techniques
MH  - Male
MH  - Oxytocin/*metabolism
MH  - Phosphodiesterase 5 Inhibitors
MH  - Piperazines/pharmacology
MH  - Pituitary Gland, Posterior/enzymology/*metabolism
MH  - Potassium Channels/metabolism
MH  - Presynaptic Terminals/*metabolism
MH  - Purines/pharmacology
MH  - Rats
MH  - Sildenafil Citrate
MH  - Sulfones/pharmacology
PMC - PMC2277045
EDAT- 2007/08/11 09:00
MHDA- 2008/01/18 09:00
PMCR- 2008/10/01
CRDT- 2007/08/11 09:00
PHST- 2007/08/11 09:00 [pubmed]
PHST- 2008/01/18 09:00 [medline]
PHST- 2007/08/11 09:00 [entrez]
PHST- 2008/10/01 00:00 [pmc-release]
AID - jphysiol.2007.139303 [pii]
AID - 10.1113/jphysiol.2007.139303 [doi]
PST - ppublish
SO  - J Physiol. 2007 Oct 1;584(Pt 1):137-47. doi: 10.1113/jphysiol.2007.139303. Epub 
      2007 Aug 9.