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Melatonin Modulates Vascular Smooth Muscle Tone

Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492

Gregory D. Goggins

Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492

Puja Agarwal

Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492

Elaine Ryan

Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492

A. John Watson

Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492

The molecular cloning of a family of melatonin receptors has created a renewed interest in the diverse actions of the hormone melatonin. The redioligand 2-[125I]iodomelatonin has identified potential sites of action for melatonin throughout the central nervous system and periphery of numerous species. Interestingly, in addition to the suprachiasmatic nucleus (the "biological clock"), 2-[125I]iodomelatonin binding sites have been localized to the rat caudal and cerebral arteries. Furthermore, in vitro, melatonin has been shown to induce a concentration-dependent vasoconstriction of rat caudal and cerebral arteries, and pig and human coronary arteries. The lack of melatonin receptor subtypeselective agonists and antagonists prevents the full pharmacological characterization of these responses. The physiological significance of the in vitro vasoconstrictive properties is far from clear, however; in rats, melatonin has been shown to reduce cerebral blood flow. The widespread use of melatonin warrants appropriately designed studies to probe the role of melatonin and its receptors in the modulation of in vitro vascular tone.

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