Ceramide Selectively Inhibits Calcium-Mediated Potentiation of β-Adrenergic-Stimulated Cyclic Nucleotide Accumulation in Rat Pinealocytes

Negishi, Tetsuo; Chik, Constance L.; Ho, Angela

doi:10.1006/bbrc.1998.8221

Cited by 12 publications

(8 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Very recently, ceramide was shown to inhibit L-type Ca 2+ channels in rat pinealocytes (21) and L-type Ca 2+ channel current in rat ventricular myocytes (22). Our findings, in the present study, are thus in line with these suggestions.…”

Section: Discussionsupporting

confidence: 93%

“…This action may be of real physiologic importance, as the biologically active concentrations of ceramide shown herein (e.g., 10 −7 to 10 −6 M) are in the range thought to be generated in vivo. The concentration of C 2 -ceramide used here for [Ca 2+ ] i measurement in cultured rat aortic smooth muscle cells (10 −7 to10 −5 M) is consistent with those used in earlier studies on HL-60 cell differentiation (1-10 µM) (17), phospholipase D inhibition in fibroblasts (10-50 µM) (18), and rat pinealocytes (10-100 µM) (21). However, the mechanism(s) for the inhibitory action of C 2 -ceramide on phenylephrine's action are not as yet fully understood.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

C₂‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca²⁺]_i in rat aortic smooth muscle

Zheng

Wang

et al. 1999

Lipids

View full text Add to dashboard Cite

In the present study, we examined the effects of cell-permeable C2-ceramide on contraction of aortic smooth muscle and intracellular free Ca2+ ([Ca2+]i). C2-ceramide (10(-7) to 10(-4) M) alone did not elicit any significant changes in either basal tension or resting levels of [Ca2+]i in rat aortic smooth muscle. However, C2-ceramide (10(-7) to 10(-4) M) attenuated phenylephrine-induced contractions in isolated rat aortic rings in a concentration-related manner, and inhibited elevations in [Ca2+]i in cultured rat aortic smooth muscle cells induced by phenylephrine. C2-ceramide-induced relaxation was found to be only slightly endothelium-dependent. However, nitric oxide inhibitors (L-NNA, L-NMMA), an inhibitor of prostanoid synthesis (indomethacin), an inhibitor of opiate actions, and several inhibitors of the pharmacologic actions of various vasoactive amines all failed to interfere with the vasorelaxant responses of C2-ceramide. Three different inhibitors of protein kinase C, when used in a wide concentration range, also failed to interfere with the ceramide-induced relaxations. Our results suggest that the sphingomyelin-signaling pathway may play an important regulatory role in arterial wall tone.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 83%

C₂‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca²⁺]_i in rat aortic smooth muscle

Zheng

Wang

et al. 1999

Lipids

View full text Add to dashboard Cite

show abstract

“…Identification of the specific ligands that can generate ceramide in rat chromaffin cells will be the subject of future studies. This search takes on added significance given the recent reports that ceramide can also modulate agonist induced cyclic AMP metabolism in both the catecholaminergic neuron-like CATH.a cell line and in rat pinealocytes (Negishi et al, 1998;See et al, 2001), because like Ca 2ϩ signaling, cAMP metabolism plays a central role in the regulation of both catecholamine secretion and biosynthesis in chromaffin cells.…”

Section: Discussionmentioning

confidence: 99%

Ceramide modulates nicotinic receptor‐dependent Ca²⁺ signaling in rat chromaffin cells

Liu

Jorgensen

Adams

et al. 2001

J of Neuroscience Research

View full text Add to dashboard Cite

Ceramide, which is an integral component of the sphingomyelin signaling pathway, can attenuate voltage-gated Ca(2+) channel (VGCC) activity in a number of cell types. The aim of the present study was to determine whether ceramide can also modulate VGCC activity, and as a consequence nicotinic receptor-dependent Ca(2+) signaling and catecholamine secretion, in rat adrenal chromaffin cells. Short-term C(6)-ceramide (CER) treatment dose-dependently inhibited nicotine (NIC)-induced peak intracellular Ca(2+) transients. Sphingomyelinase elicited similar responses, whereas the inactive ceramide analog C(2)-dihydroceramide had no effect on NIC-induced Ca(2+) transients. CER suppressed KCl- and NIC-induced Ca(2+) transients to a similar extent, suggesting that the voltage-gated Ca(2+) channel was a primary site of inhibition. In direct support of this concept, whole-cell patch-clamp analysis demonstrated that CER and sphingomyelinase significantly reduced peak Ca(2+) currents. Pretreatment with staurosporine significantly attenuated CER-dependent inhibition of both NIC-induced Ca(2+) transients and peak Ca(2+) current, suggesting that the effects of CER are mediated at least in part by protein kinase C. Consistent with suppressed Ca(2+) signaling, CER also significantly inhibited NIC-induced catecholamine secretion measured at the single-cell level by carbon fiber amperometry. This effect of CER was also significantly attenuated by pretreatment with staurosporine These data demonstrate that the sphingomyelin signaling pathway can modulate nicotinic receptor-dependent Ca(2+) signaling and catecholamine secretion in rat chromaffin cells.

show abstract

“…It should be mentioned that ceramide has previously been shown to increase intracellular cAMP accumulation in rat pinealocytes by inhibiting its synthesis (29). This is suggested by the study in which IBMX was used to inhibit phosphodiesterase activities.…”

Section: Discussionmentioning

confidence: 99%

Ceramide Enhances Growth Hormone (GH)-Releasing Hormone-Stimulated Cyclic Adenosine 3′,5′-Monophosphate Accumulation but Inhibits GH Release in Rat Anterior Pituitary Cells¹

Negishi

Chik

1999

Endocrinology

View full text Add to dashboard Cite

In this study, the effect of ceramide on GH-releasing hormone (GHRH)-stimulated cAMP accumulation and GH release in rat anterior pituitary cells was investigated. C2-, C6-, and C8-ceramide were found to enhance GHRH-stimulated cAMP accumulation. In contrast, their effects on GHRH-stimulated GH release were inhibitory. Treatment with a glucosylceramide synthase inhibitor produced a similar enhancing effect on cAMP accumulation and an inhibitory effect on GH release. To identify the pathway through which ceramide mediated its effect, it was found that ceramide inhibited GH release stimulated by KCl, BayK 8644, and a GH-releasing peptide, but not that stimulated by ionomycin or an activator of protein kinase C. Direct measurement of intracellular Ca2+ revealed that C2-ceramide inhibited GHRH- and KCl-mediated increases in intracellular Ca2+, suggesting that ceramide probably inhibits GH release through inhibition of the L-type Ca2+ channels. As for its mechanism on cAMP accumulation, the enhancing effect of ceramide on GHRH-stimulated cAMP accumulation was abolished in the presence of a phosphodiesterase inhibitor, isobutylmethylxanthine, suggesting that ceramide enhances the cAMP response through inhibition of its metabolism. Taken together, our results suggest that ceramide plays an important role in the regulation of GHRH-stimulated responses in somatotrophs. By reducing GH secretion while enhancing cAMP accumulation, ceramide may promote the synthesis and storage of GH in rat anterior pituitary cells.

show abstract

Ceramide Selectively Inhibits Calcium-Mediated Potentiation of β-Adrenergic-Stimulated Cyclic Nucleotide Accumulation in Rat Pinealocytes

Cited by 12 publications

References 23 publications

C₂‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca²⁺]_i in rat aortic smooth muscle

C₂‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca²⁺]_i in rat aortic smooth muscle

Ceramide modulates nicotinic receptor‐dependent Ca²⁺ signaling in rat chromaffin cells

Ceramide Enhances Growth Hormone (GH)-Releasing Hormone-Stimulated Cyclic Adenosine 3′,5′-Monophosphate Accumulation but Inhibits GH Release in Rat Anterior Pituitary Cells¹

Contact Info

Product

Resources

About

Ceramide Selectively Inhibits Calcium-Mediated Potentiation of β-Adrenergic-Stimulated Cyclic Nucleotide Accumulation in Rat Pinealocytes

Cited by 12 publications

References 23 publications

C2‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca2+]i in rat aortic smooth muscle

C2‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca2+]i in rat aortic smooth muscle

Ceramide modulates nicotinic receptor‐dependent Ca2+ signaling in rat chromaffin cells

Ceramide Enhances Growth Hormone (GH)-Releasing Hormone-Stimulated Cyclic Adenosine 3′,5′-Monophosphate Accumulation but Inhibits GH Release in Rat Anterior Pituitary Cells1

Contact Info

Product

Resources

About

C₂‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca²⁺]_i in rat aortic smooth muscle

C₂‐ceramide attenuates phenylephrine‐induced vasoconstriction and elevation in [Ca²⁺]_i in rat aortic smooth muscle

Ceramide modulates nicotinic receptor‐dependent Ca²⁺ signaling in rat chromaffin cells

Ceramide Enhances Growth Hormone (GH)-Releasing Hormone-Stimulated Cyclic Adenosine 3′,5′-Monophosphate Accumulation but Inhibits GH Release in Rat Anterior Pituitary Cells¹