The role of the nitric oxide-cGMP signal transduction pathway in gastrointestinal smooth muscle function during pregnancy.

We previously showed that plasma membrane Ca2+-ATPase (PMCA) activity accounted for 25–30% of relaxation in bladder smooth muscle ( 8 ). Among the four PMCA isoforms only PMCA1 and PMCA4 are expressed in smooth muscle. To address the role of these isoforms, we measured cytosolic Ca2+ ([Ca2+]i) using fura-PE3 and simultaneously measured contractility in bladder smooth muscle from wild-type (WT), Pmca1+/−, Pmca4+/−, Pmca4−/−, and Pmca1+/− Pmca4−/− mice. There were no differences in basal [Ca2+]i values between bladder preparations. KCl (80 mM) elicited both larger forces (150–190%) and increases in [Ca2+]i (130–180%) in smooth muscle from Pmca1+/− and Pmca1+/− Pmca4−/− bladders than those in WT or Pmca4−/−. The responses to carbachol (CCh: 10 μM) were also greater in Pmca1+/− (120–150%) than in WT bladders. In contrast, the responses in Pmca4−/− and Pmca1+/− Pmca4−/− bladders to CCh were significantly smaller (40–50%) than WT. The rise in half-times of force and [Ca2+]i increases in response to KCl and CCh, and the concomitant half-times of their decrease upon washout of agonist were prolonged in Pmca4−/− (130–190%) and Pmca1+/− Pmca4−/− (120–250%) bladders, but not in Pmca1+/− bladders with respect to WT. Our evidence indicates distinct isoform functions with the PMCA1 isoform involved in overall Ca2+ clearance, while PMCA4 is essential for the [Ca2+]i increase and contractile response to the CCh receptor-mediated signal transduction pathway.

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Role of Caveolin‐1 in Gastrointestinal Smooth Muscle Function

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.888.1 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Chereena T Clay ◽

Sunila Mahavadi

Keyword(s):

Smooth Muscle ◽

Muscle Function ◽

Caveolin 1 ◽

Gastrointestinal Smooth Muscle ◽

Smooth Muscle Function

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The nitric oxide-cyclic GMP signal transduction pathway in vascular smooth muscle preparations and other tissues

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)59907-3 ◽

1992 ◽

Vol 58 ◽

pp. 150-157

Author(s):

F. Murad ◽

U. Forstermann ◽

M. Nakane ◽

H. Schmidt ◽

J. Pollock ◽

...

Keyword(s):

Nitric Oxide ◽

Signal Transduction ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Cyclic Gmp ◽

Signal Transduction Pathway ◽

Transduction Pathway

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NMDA and nitric oxide act through the cGMP signal transduction pathway to repress hypothalamic gonadotropin-releasing hormone gene expression.

The EMBO Journal ◽

10.1002/j.1460-2075.1996.tb00386.x ◽

1996 ◽

Vol 15 (3) ◽

pp. 538-547 ◽

Cited By ~ 48

Author(s):

D. D. Belsham ◽

W. C. Wetsel ◽

P. L. Mellon

Keyword(s):

Gene Expression ◽

Nitric Oxide ◽

Signal Transduction ◽

Signal Transduction Pathway ◽

Gonadotropin Releasing Hormone ◽

Transduction Pathway ◽

Releasing Hormone ◽

Cgmp Signal

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GABAAand GABACreceptor antagonists increase retinal cyclic GMP levels through nitric oxide synthase

Visual Neuroscience ◽

10.1017/s0952523803206052 ◽

2003 ◽

Vol 20 (6) ◽

pp. 627-637 ◽

Cited By ~ 9

Author(s):

DOU YU ◽

WILLIAM D. ELDRED

Keyword(s):

Nitric Oxide ◽

Signal Transduction ◽

Receptor Antagonist ◽

Cyclic Gmp ◽

Gaba Receptor ◽

Signal Transduction Pathway ◽

Receptor Antagonists ◽

Cgmp Signal ◽

Oxide Synthase

The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signal transduction pathway plays a role in every retinal cell type. Previous studies have shown that excitatory glutamatergic synaptic pathways can increase cGMP-like immunoreactivity (cGMP-LI) in retina through stimulation of NO production, but little is known about the role of synaptic inhibition in the modulation of cGMP-LI. Gamma-amino-n-butyric acid (GABA) plays critical roles in modulating excitatory synaptic pathways in the retina. Therefore, we used GABA receptor antagonists to explore the role of GABAergic inhibitory synaptic pathways on the modulation of the NO/cGMP signal-transduction system. Cyclic GMP immunocytochemistry was used to investigate the effects of the GABA receptor antagonists bicuculline, picrotoxin, and (1,2,5,6-tetrahyropyridin-4-yl) methylphosphinic acid (TPMPA) on levels of cGMP-LI. Cyclic GMP-LI was strongly increased in response to the GABAAreceptor antagonist bicuculline, while the GABACreceptor antagonist TPMPA had little effect on cGMP-LI. The GABAA/GABACreceptor antagonist, picrotoxin, caused a moderate increase in cGMP-LI, which was mimicked by the combination of bicuculline and TPMPA. The nitric oxide synthase inhibitor, S-methyl-L-thiocitrulline (SMTC), blocked the increased cGMP-LI in response to stimulation with either bicuculline or picrotoxin. Treatments with either of the glutamate receptor antagonists (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) partially blocked the increases in cGMP-LI seen in response to bicuculline, but a combination of MK-801 and CNQX completely eliminated these increases. These results suggest that inhibitory synaptic pathways involving both types of GABA receptors work through excitatory glutamatergic receptors to regulate the NO/cGMP signal-transduction pathway in retina.

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