Melatonin attenuates rat carotid chemoreceptor response to hypercapnic acidosis.

Abstract

Respiratory activity is under circadian modulation and the physiological mechanisms may involve the pineal secretory product, melatonin, and the carotid chemoreceptor. We hypothesized that melatonin modulates the carotid chemoreceptor response to hypercapnic acidosis. To determine whether the effect of melatonin on the chemoreceptor response to hypercapnic acidosis is mediated by melatonin receptors in the chemosensitive cells, cytosolic calcium ([Ca2+]i) was measured by spectrofluorometry in fura-2-loaded glomus cells dissociated from rat carotid bodies. Melatonin (0.01-10 nm) per se did not change the [Ca2+]i levels of the glomus cells but it concentration-dependently attenuated the peak [Ca2+]i response to hypercapnic acidosis in the glomus cells. In addition, the [Ca2+]i response was attenuated by 2-iodomelatonin, an agonist of melatonin receptors. The melatonin-induced attenuation of the [Ca2+]i response to hypercapnic acidosis was abolished by pretreatment with an non-selective mt1/MT2 antagonist, luzindole, and by MT2 antagonists, 4-phenyl-2-propionamidotetraline or DH97. In situ hybridization study with antisense mt1 and MT2 receptor mRNA oligonucleotide probes showed an expression of mt1 and MT2 receptors in the rat carotid body. Also, melatonin attenuated the carotid afferent response to hypercapnic acidosis in single- or pauci-fibers recorded from the sinus nerve in isolated carotid bodies superfused with bicarbonate-buffer saline. Results suggest that an activation of the melatonin receptors expressed in the glomus cells of the rat carotid body reduces the chemoreceptor response to hypercapnic acidosis. This modulation may play a physiological role in the influence of the circadian rhythms on the chemoreflex.

• Authors: Yung Wui Tjong, Yueping Chen, Emily C Liong, Shing Fat Ip, George L Tipoe, Man Lung Fung
• Journal: Journal of pineal research (J Pineal Res) Vol. 36 Issue 1 Pg. 49-57 (Jan 2004) ISSN: 0742-3098 [Print] England
• PMID: 14675130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-phenyl-2-propionamidotetraline
• N-pentanoyl-2-benzyltryptamine
• Receptor, Melatonin, MT1
• Receptor, Melatonin, MT2
• Receptors, Melatonin
• Tetrahydronaphthalenes
• Tryptamines
• luzindole
• 2-iodomelatonin
• Melatonin
• Calcium
• Fura-2

Topics

• Acidosis, Respiratory (drug therapy, metabolism)
• Animals
• Calcium (metabolism)
• Carotid Body (cytology, drug effects, metabolism)
• Chemoreceptor Cells (drug effects)
• Electrophysiology (methods)
• Fura-2 (metabolism)
• Hypercapnia (drug therapy, metabolism)
• Melatonin (analogs & derivatives, antagonists & inhibitors, pharmacology, physiology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Melatonin, MT1 (antagonists & inhibitors, genetics, metabolism)
• Receptor, Melatonin, MT2 (antagonists & inhibitors, genetics, metabolism)
• Receptors, Melatonin (antagonists & inhibitors, drug effects)
• Tetrahydronaphthalenes (pharmacology)
• Tryptamines (pharmacology)