Nitric oxide donor-induced apoptosis in smooth muscle cells is modulated by protein kinase C and protein kinase A

Abstract Although the uterus is a target tissue for LH and its homologue hCG the second messenger system responding to LH/hCG in myometrial cells is not established. In this study we investigated the involvement of protein kinase A and protein kinase C in the action of hCG on porcine myometrial smooth muscle cells in vitro. Myometrium was obtained from ovariectomized gilts given 2·5 mg oestradiol benzoate plus 50 mg progesterone for five consecutive days. Myometrial cells were cultured for 48 h and different doses of hCG were then added. Increasing doses of hCG stimulated concentration-dependent increases in [3H]inositol phosphates (IPs) accumulation in incubations lasting 24 h. The highest dose of hCG (1000 mU/ml) increased turnover of IPs by 2·4-fold as reflected in elevations in IP1, IP2 and IP3, and similar effects were observed with noradrenaline. The time- and concentration-dependent effects of hCG on IPs accumulation occurred between 16 and 24 h of incubation. Incubation of myocytes with the lowest doses of hCG (0·1 and 1 mU/ml) caused a significant increase in cAMP accumulation but the highest doses (10–1000 mU/ml) had no effect on cAMP concentrations. This is the first demonstration that LH/hCG receptor signalling leads to increased inositol phosphate turnover in myometrial cells as well as cAMP generation and it leads to the conclusion that both protein kinase A and protein kinase C signalling mechanisms are involved in gonadotrophin action in porcine myometrial smooth muscle cells. Journal of Endocrinology (1996) 148, 175–180

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Protein kinase C and protein kinase A regulate the expression of angiotensin II receptor mRNA in smooth muscle cells

European Journal of Pharmacology Molecular Pharmacology ◽

10.1016/0922-4106(94)90169-4 ◽

1994 ◽

Vol 267 (2) ◽

pp. 175-183 ◽

Cited By ~ 10

Author(s):

Xi Chen ◽

Junji Nishimura ◽

Jahan Hasna ◽

Sei Kobayashi ◽

Tomomi Shikasho ◽

...

Keyword(s):

Smooth Muscle ◽

Protein Kinase C ◽

Angiotensin Ii ◽

Protein Kinase ◽

Smooth Muscle Cells ◽

Protein Kinase A ◽

Angiotensin Ii Receptor ◽

Receptor Mrna ◽

Kinase C ◽

Kinase A

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Vasoconstrictors inhibit ATP-sensitive K+ channels in arterial smooth muscle through protein kinase C.

The Journal of General Physiology ◽

10.1085/jgp.108.4.315 ◽

1996 ◽

Vol 108 (4) ◽

pp. 315-323 ◽

Cited By ~ 88

Author(s):

A D Bonev ◽

M T Nelson

Keyword(s):

Smooth Muscle ◽

Protein Kinase C ◽

Protein Kinase ◽

Smooth Muscle Cells ◽

Protein Kinase A ◽

Katp Channels ◽

Muscle Cells ◽

Kinase C ◽

Calcitonin Gene ◽

Kinase A

The effects of vasoconstrictor-receptor (neuropeptide Y, alpha-adrenergic, serotonergic, histaminergic) stimulation on currents through ATP-sensitive potassium (KATP) channels in arterial smooth muscle cells were examined. Whole-cell KATP currents, activated by the synthetic KATP channel opener pinacidil or by the endogenous vasodilator, calcitonin gene-related peptide, which acts through protein kinase A, were measured in smooth muscle cells isolated from mesenteric arteries of rabbit. Stimulation of NPY-, alpha 1-, serotonin (5-HT2)-, and histamine (H1)-receptors inhibited KATP currents by 40-56%. The signal transduction pathway that links these receptors to KATP channels was investigated. An inhibitor of phospholipase C (D609) and of protein kinase C (GF 109203X) reduced the inhibitory effect of these vasoconstrictors on KATP currents from 40-56% to 11-23%. Activators of protein kinase C, a diacylglycerol analogue and phorbol 12-myristate 13-acetate (PMA), inhibited KATP currents by 87.3 and 84.2%, respectively. KATP currents, activated by calcitonin gene-related peptide, were also inhibited (47-87%) by serotonin, phenylephrine, and PMA. We propose that KATP channels in these arterial myocytes are subject to dual modulation by protein kinase C (inhibition) and protein kinase A (activation).

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