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

Abstract

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.

Activation of submucosal 5‐HT3 receptors elicits a somatostatin‐dependent inhibition of ion secretion in rat colon

“…This antibody identified a single band of 54 kDa by Western blotting in the rat cardiomyocytes (Bell et al, 2008). Ablation of sst2 receptor immunoreactivity (IR) by omitting the primary antibody of sst2 receptor or by preadsorption with an excess of the corresponding synthetic peptide confirmed the specificity of the antibody (data not shown).…”

Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection

“…This finding is supported by earlier data showing that SST protects against retinal ischemia/ reperfusion injury in a mouse model (Wang et al, 2017) and implies that SST may have a general anti-ischemic effect in a variety of cells. All Sstrs were described in both rat cardiomyocytes and H9C2 cell lines, although only the expression of Sstr3, Sstr4, and Sstr5 was abundant (Granata et al, 2004;Bell et al, 2008). Accordingly, SST and a related peptide, cortistatin-14, and the synthetic SSTR2, SSTR3, and SSTR5 agonist octreotide significantly reduce brain infarct size in a middle cerebral artery occlusion model (Rauca et al, 1999).…”

The control of cardiac ventricular excitability by autonomic pathways

“…Thus agonist activation of these pathways is positively inotropic (Levi et al, 1975;Christophe et al, 1984;Alloatti et al, 1991). In addition to the M2 muscarinic receptor there are receptors for somatostatin and sphingosine-1-phosphate that couple to inhibitory Gproteins (Bell et al, 2008;Ochi et al, 2006). GPCRs for endothelin (ET-A) and angiotensin II (AT-1) are present in ventricular cells and these couple to G q\11 leading to modest positively inotropic effects and cardiac hypertrophy (Pieske et al, 1999;Regitz-Zagrosek et al, 1995;Sugden and Clerk, 1998).…”