Role of peripheral 5-HT5A receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats.

Abstract

5-HT inhibits cardiac sympathetic neurotransmission in normoglycaemic rats, via 5-HT1B, 5-HT1D and 5-HT5A receptor activation. Since type 1 diabetes impairs the cardiac sympathetic innervation leading to cardiopathies, this study aimed to investigate whether the serotonergic influence on cardiac noradrenergic control is altered in type 1 diabetic rats. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by electrical preganglionic stimulation (C7-T1) of the cardioaccelerator sympathetic outflow or i.v. noradrenaline bolus injections. Immunohistochemistry was performed to study 5-HT1B, 5-HT1D and 5-HT5A receptor expression in the stellate ganglion from normoglycaemic and diabetic rats. In the diabetic group, i) i.v. continuous infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT1/5A agonist 5-carboxamidotryptamine (without modifying noradrenaline-induced tachycardia), but not by the agonists indorenate (5-HT1A), CP 93,129 (5-HT1B), PNU 142633 (5-HT1D), or LY344864 (5-HT1F); ii) SB 699551 (5-HT5A antagonist; i.v.) completely reversed 5-CT-induced cardiac sympatho-inhibition; and iii) 5-HT5A receptors were more expressed in the stellate ganglion compared to normoglycaemic rats. These results show the prominent role of the peripheral 5-HT5A receptors prejunctionally inhibiting the cardiac sympathetic drive in type 1 diabetic rats.

• Authors: José Ángel García-Pedraza, Oswaldo Hernández-Abreu, Asunción Morán, José Carretero, Mónica García-Domingo, Carlos M Villalón
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 19358 (11 09 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 33168874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• Carbazoles
• Chromans
• Fluorobenzenes
• LY 344864
• Pyridines
• Pyrroles
• Receptor, Serotonin, 5-HT1B
• Receptor, Serotonin, 5-HT1D
• Receptors, Serotonin
• SB-699551-A
• serotonin 5 receptor
• 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one
• Serotonin
• 5-Methoxytryptamine
• 5-carboxamidotryptamine
• indorenate
• PNU 142633F
• Norepinephrine

Topics

• 5-Methoxytryptamine (analogs & derivatives, pharmacology)
• Animals
• Biphenyl Compounds (pharmacology)
• Carbazoles (pharmacology)
• Chromans (pharmacology)
• Diabetes Mellitus, Experimental (chemically induced, metabolism)
• Diabetes Mellitus, Type 1 (chemically induced, metabolism)
• Electric Stimulation Therapy
• Fluorobenzenes (pharmacology)
• Immunohistochemistry
• Male
• Norepinephrine (pharmacology)
• Pyridines (pharmacology)
• Pyrroles (pharmacology)
• Rats
• Rats, Wistar
• Receptor, Serotonin, 5-HT1B (physiology)
• Receptor, Serotonin, 5-HT1D (physiology)
• Receptors, Serotonin (physiology)
• Serotonin (analogs & derivatives, chemistry, metabolism)
• Sympathetic Nervous System (physiology)