Expression of cyclic AMP-dependent protein kinase isoforms in human cavernous arteries: functional significance and relation to phosphodiesterase type 4.
BACKGROUND
The cyclic adenosine monophosphate-dependent protein kinase (cAK) is considered a key protein in the control of smooth muscle tone in the cardiovascular system. There is evidence that erectile dysfunction might be linked to systemic vascular disorders and arterial insufficiency, subsequently resulting in structural changes in the penile tissue. The expression and significance of cAK in human cavernous arteries (HCA) have not been evaluated.


OBJECTIVE
To evaluate the expression of cAK isoforms in HCA and examine the role of cAK in the cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-mediated control of penile vascular smooth muscle.


METHODS
The expression and distribution of phosphodiesterase type 4 (PDE4) and cAK isoforms in sections of HCA were investigated by means of immunohistochemistry and Western blot analysis. The effects of the cAK inhibitor Rp-8-CPT-cAMPS on the relaxation of isolated preparations of HCA (diameter > 100 µm) induced by rolipram, sildenafil, tadalafil, and vardenafil were studied using the organ bath technique.


METHODS
Investigate the expression of cAK in relation to α-actin and PDE4 in HCA and evaluate the effects of an inhibition of cAK on the relaxation induced by inhibitors of PDE4 and PDE5 of isolated penile arteries.


RESULTS
Immunosignals specific for cAKIα, IIα, and IIβ were observed within the wall of HCA. Double stainings revealed colocalization of cAK with α-actin and PDE4. The expression of cAK isoforms was confirmed by Western blot analysis. The reversion of tension induced by inhibitors of PDE4 and PDE5 of isolated penile vascular tissue were attenuated significantly by Rp-8-CPT-cAMPS.


CONCLUSIONS
Our results demonstrate the expression of cAK isoforms in the smooth musculature of HCA and its colocalization with PDE4. A significant role for cAK in the regulation mediated by cAMP and cGMP of vascular smooth muscle tone in HCA can also be assumed.
Waldkirch
Eginhard S
ES
Hannover Medical School-Division of Surgery, Department of Urology and Urological Oncology, Hannover, Germany.
Ückert
Stefan
S
Hannover Medical School-Division of Surgery, Department of Urology and Urological Oncology, Hannover, Germany. Electronic address: streetgang@gmx.de.
Sigl
Katja
K
MorphoSys AG, Martinsried, Germany.
Satzger
Imke
I
Hannover Medical School-Department of Dermatology and Allergology, Hannover, Germany.
Geismar
Ulrike
U
Private Dermatological Practice, Hannover, Germany.
Langnäse
Kristina
K
Otto-von-Guericke-University, Faculty of Medicine-Institute for Biochemistry and Cell Biology, Magdeburg, Germany.
Richter
Karin
K
Otto-von-Guericke-University, Faculty of Medicine-Institute for Biochemistry and Cell Biology, Magdeburg, Germany.
Sohn
Michael
M
Frankfurter Diakonie-Kliniken, St. Markus Academic Hospital-Department of Urology, Frankfurt am Main, Germany.
Kuczyk
Markus A
MA
Hannover Medical School-Division of Surgery, Department of Urology and Urological Oncology, Hannover, Germany.
Hedlund
Petter
P
University Vita Salute, Faculty of Medicine, San Raffaele Hospital-Department of Urology, Urological Research Institute, Milan, Italy.
D000199:Actins / Q000502:physiology; D000328:Adult; D001158:Arteries / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000502:physiology*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010413:Penis / Q000098:blood supply*; D020033:Protein Isoforms / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D000199:Actins; D020033:Protein Isoforms; D017868:Cyclic AMP-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D000095043:Cyclin-Dependent Kinase-Activating Kinase