Defective smooth muscle regulation in cGMP kinase I-deficient mice.
Regulation of smooth muscle contractility is essential for many important biological processes such as tissue perfusion, cardiovascular haemostasis and gastrointestinal motility. While an increase in calcium initiates smooth muscle contraction, relaxation can be induced by cGMP or cAMP. cGMP-dependent protein kinase I (cGKI) has been suggested as a major mediator of the relaxant effects of both nucleotides. To study the biological role of cGKI and its postulated cross-activation by cAMP, we inactivated the gene coding for cGKI in mice. Loss of cGKI abolishes nitric oxide (NO)/cGMP-dependent relaxation of smooth muscle, resulting in severe vascular and intestinal dysfunctions. However, cGKI-deficient smooth muscle responded normally to cAMP, indicating that cAMP and cGMP signal via independent pathways, with cGKI being the specific mediator of the NO/cGMP effects in murine smooth muscle.
Pfeifer
A
A
Institut für Pharmakologie und Toxikologie, München, Biedersteiner, Str. 29, 80802 Müchen, Germany.
Klatt
P
P
Massberg
S
S
Ny
L
L
Sausbier
M
M
Hirneiss
C
C
Wang
G X
GX
Korth
M
M
Aszódi
A
A
Andersson
K E
KE
Krombach
F
F
Mayerhofer
A
A
Ruth
P
P
Fässler
R
R
Hofmann
F
F
D000818:Animals; D001013:Aorta, Thoracic; D002469:Cell Separation; D046508:Culture Techniques; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D005748:Gastric Fundus / Q000201:enzymology / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000235:genetics; D018390:Gene Targeting; D007413:Intestinal Mucosa / Q000201:enzymology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics*; D009130:Muscle, Smooth / Q000201:enzymology* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D015398:Signal Transduction
D009569:Nitric Oxide; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP