Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts

Smith, William G.; Nair, R. Unnikrishnan; Adamson, Dawn; Kearney, Mark T.; Ball, Stephen G.; Balmforth, Anthony J.

doi:10.1677/joe.1.06082

Cited by 50 publications

(37 citation statements)

References 41 publications

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“…To date, the majority of research on somatostatin has focused on hormonal regulation in gastrointestinal and nervous systems. More recent evidence has suggested the presence of the somatostatin receptors in both human hearts and H9c2 cardiac muscle cells (10,30). Somatostatin was found to suppress atrial contractile function and blunt atrioventricular conduction (1).…”

mentioning

confidence: 99%

Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

Hua

Ma²,

Samson³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Hua Y, Ma H, Samson WK, Ren J. Neuronostatin inhibits cardiac contractile function via a protein kinase A-and JNK-dependent mechanism in murine hearts. Am J Physiol Regul Integr Comp Physiol 297: R682-R689, 2009. First published June 24, 2009 doi:10.1152/ajpregu.00196.2009.-Neuronostatin, a newly identified peptide hormone sharing the same precursor with somatostatin, exerts multiple pharmacological effects in gastrointestinal tract, hypothalamus, and cerebellum. However, the cardiovascular effect of neuronostatin is unknown. The aim of this study was to elucidate the impact of neuronostatin on cardiac contractile function in murine hearts and isolated cardiomyocytes. Short-term exposure of neuronostatin depressed left ventricular developed pressure (LVDP), maximal velocity of pressure development (ϮdP/dt), and heart rate in Langendorff heart preparation. Consistently, neuronostatin inhibited peak shortening (PS) and maximal velocity of shortening/relengthening (ϮdL/dt) without affecting time-to-PS (TPS) and time-to-90% relengthening (TR 90) in cardiomyocytes. The neuronostatin-elicited cardiomyocyte mechanical responses were mimicked by somatostatin, the other posttranslational product of preprosomatostatin. Furthermore, the neuronostatin-induced cardiomyocyte mechanical effects were ablated by the PKA inhibitor H89 (1 M) and the Jun N-terminal kinase (JNK) inhibitor SP600125 (20 M). The PKC inhibitor chelerythrine (1 M) failed to alter neuronostatin-induced cardiomyocyte mechanical responses. To the contrary, chelerythrine, but not H89, abrogated somatostatin-induced cardiomyocyte contractile responses. Our results also showed enhanced c-fos and c-jun expression in response to neuronostatin exposure (0.5 to 2 h). Taken together, our data suggest that neuronostatin is a peptide hormone with overt cardiac depressant action. The neuronostatin-elicited cardiac contractile response appears to be mediated, at least in part, through a PKA-and/or JNK-dependent mechanism.neuronostatin; cardiomyocytes; contraction; protein kinase; cell signaling SOMATOSTATIN [ALSO NAMED SOMATOTROPIN release-inhibiting factor or growth hormone inhibiting hormone], is a peptide hormone first found in the hypothalamus. It is also expressed in neuroendocrine organs, gastrointestinal tract, thyroid and adrenal glands, liver, spleen, kidney, prostate, inflammatory, and immune cells (23). Somatostatin has been shown to be involved in the regulatory processes of endocrine system, neurotransmission, cell proliferation, hormone secretion, and cardiovascular function (17). This peptide hormone contains two active isoforms (with 14 amino acids and 28 amino acids) produced by alternative cleavage of a single preproprotein. These two isoforms of somatostatin are capable of activating five related G protein-coupled membrane receptors with different affinity (9,31,32). To date, the majority of research on somatostatin has focused on hormonal regulation in gastrointestinal and nervous systems. More recent evidence has suggested the presence of the som...

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confidence: 99%

Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

Hua

Ma²,

Samson³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Using a similar approach, other investigators have been unable to detect SRIF1B (SSTR5) [38] or SRIF2B (SSTR4) [30] receptor expression in adult murine heart. In a study by Smith and co-workers [33], human cardiomyocytes were found to express only SRIF1A (SSTR2) and SRIF2A (SSTR1) receptors, in contrast to human cardiac fibroblasts, which in addition to these subtypes, expressed SRIF1B (SSTR5) and SRIF2B (SSTR4) but not SRIF1C (SSTR3) receptors. Rodent and human myocardium clearly differ in regard to SRIF receptor subtype expression, since we have found that SRIF1A (SSTR2) and SRIF2A (SSTR1) are the least abundant receptors expressed in adult rat ventricular cardiomyocytes.…”

Section: Hypertrophic Parametersmentioning

confidence: 95%

“…Left ventricular hypertrophy in acromegaly is characterized not only by hypertrophy of cardiomyocytes, which are terminally differentiated and unable to proliferate, but also disproportionate proliferation of cardiac fibroblasts and accumulation of fibrillar collagen contributing to impaired diastolic function [13,14]. In view of the presence of SRIF (SSTR) receptors on human cardiac fibroblasts [33] a direct inhibitory influence of SRIF-14 analogues on fibroblast proliferation cannot be discounted at present.…”

Section: Hypertrophic Parametersmentioning

confidence: 99%

“…The embryonic rat cardiomyocyte cell line H9c2 expresses all five SRIF (SSTR) receptors [31], while expression of SRIF1B (SSTR5) mRNA can be induced in neonatal cardiomyocytes in response to the cytokine, leukemia inhibitory factor [32]. Smith and coworkers [33] have recently reported the presence of SRIF1A (SSTR2), SRIF1B (SSTR5), SRIF2A (SSTR1) and SRIF2B (SSTR4), but not SRIF1C (SSTR3) receptor mRNA in both atrial and ventricular tissues from human heart; while cardiac fibroblasts expressed all four of these receptors, cardiomyocyte expression was restricted to SRIF1A (SSTR2) and SRIF2A (SSTR1).…”

Section: Introductionmentioning

confidence: 99%

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SRIF Receptor Subtype Expression and Involvement in Positive and Negative Contractile Effects of Somatostatin-14 (SRIF-14) in Ventricular Cardiomyocytes

Bell¹,

Zhao²,

McMaster³

et al. 2008

Cell Physiol Biochem

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Background/Aims: Somatostatin-14 (SRIF-14), a neuropeptide co-stored with acetylcholine in the cardiac parasympathetic innervation, exerts both positive and negative influences directly on contraction of ventricular cardiomyocytes, indicative of involvement of more than one of five known SRIF (SSTR) receptor subtypes. The aim was to characterize receptor subtype expression in adult rat ventricular cardiomyocytes and to investigate the influence of a series of SRIF (SSTR) subtype-selective agonists on contractile parameters. Methods: mRNA and protein expression of each receptor subtype were quantified by RT-PCR and immunoblotting respectively; for contraction studies, cells were stimulated at 0.5 Hz under basal conditions and in the presence of isoprenaline (ISO, 10^-8M). Results: all five SRIF (SSTR) receptor subtypes were expressed in cardiomyocytes although SRIF1A (SSTR2) and SRIF2A (SSTR1) were less abundant than the other subtypes. L803087 (10^-8M), a SRIF2B (SSTR4) agonist, attenuated ISO-stimulated peak contractile amplitude and prolonged relaxation time (T₅₀). L796778 (10^-7M), a SRIF1C (SSTR3) agonist, augmented basal and ISO-stimulated peak contractile amplitude; L779976 (10^-8M) and L817818 (10^-9M), agonists at SRIF1A (SSTR2) and SRIF1B (SSTR5) receptors, respectively, also augmented ISO-stimulated peak amplitude. Conclusion: these data support involvement of SRIF2B (SSTR4) receptors in the negative contractile effects of SRIF-14, while one or more of the three SRIF1 receptor subtypes (SSTR2, 3 or 5) may contribute to the positive contractile effects of SRIF-14.

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“…Octreotide has anti-secretive and anti-proliferative effects by binding and activating somatostatin receptor subtypes 2 and 5 [5]. These receptors are expressed in human cardiac myocytes and fibroblasts [11]. Octreotide improves LV hypertrophy, LV function and ventricular arrhythmia in patients with acromegaly [12][13][14].…”

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confidence: 99%

The temporary drop of serum octreotide concentration deteriorated ventricular tachycardia in an acromegalic patient

et al. 2013

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CARDIOVASCULAR DISEASE is a major cause of morbidity and mortality in patients with acromegaly [1]. The most common feature of acromegalic cardiomyopathy is a concentric biventricular hypertrophy. There are specific structural changes in the myocardium with increased cardiac myocyte size and interstitial fibrosis of both ventricles [2]. Actually, the postmortem studies revealed left ventricular hypertrophy (LVH) in more than 90% of acromegalic patients with long disease duration [2]. Hypertrophic cardiomyopathy (HCM) is characterized by LVH with a nondilated chamber. About 10 % of them evolve into dilated phase of HCM that is characterized by systolic dysfunction, dilatation of the LV and LV wall thickness. Dilated phase of HCM is associated with an increased incidence of ventricular tachycardia (VT) [3].The temporary drop of serum octreotide concentration deteriorated ventricular tachycardia in an acromegalic patient Abstract. Acromegaly is frequently accompanied by left ventricular hypertrophy (LVH) which causes ventricular dysfunction. Ventricular arrhythmia is one of the important complications in acromegalic patients. Hypertrophic cardiomyopathy (HCM) is characterized by LVH with a nondilated chamber. About 10 % of HCM evolve into dilated phase of HCM, which is associated with an increased incidence of ventricular tachycardia (VT). However there is no report about a combination of dilated phase of HCM and VT in acromegalic patients. Octreotide is a somatostatin analog that has been used for medical therapy for acromegaly. We herein report that the first case of the change of serum octreotide concentration affected the control of VT, which was induced by dilated phase of HCM. A 56-year-old Japanese man was referred to our hospital for treatment of acromegaly. The patient was diagnosed the dilated phase of HCM with sustained VT. The frequency and severity of VT were gradually ameliorated by subcutaneous octreotide injection. However VT was deteriorated when its injection was changed to octreotide long-acting release (LAR) injection. The temporary drop in serum octreotide concentration was known at the transition from subcutaneous injection to LAR injection. This clinical course gives us the important information that subcutaneous octreotide injection for two weeks should be necessary to keep serum octreotide concentration when switing to octreotide LAR administration in acromegalic patients with severe arrhythmia.

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Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts

Cited by 50 publications

References 41 publications

Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

SRIF Receptor Subtype Expression and Involvement in Positive and Negative Contractile Effects of Somatostatin-14 (SRIF-14) in Ventricular Cardiomyocytes

The temporary drop of serum octreotide concentration deteriorated ventricular tachycardia in an acromegalic patient

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