Differential Expression of Melatonin Receptors in Spontaneously Hypertensive Rats

Viswanathan, Mohan; Laitinen, Jarmo T.; Saavedra, Juan M.

doi:10.1159/000126318

Cited by 38 publications

(25 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…125 I]iodomelatonin, a nonselective MT 1 /MT 2 radioligand, in the medial layer of caudal and cerebral arteries (Viswanathan et al, 1990(Viswanathan et al, , 1992. This binding, however, likely reflects MT 1 melatonin receptors because the density of endogenous MT 2 receptors is generally too low in mammalian tissues to be detected by receptor autoradiography (Liu et al, 1997;.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MT₂Melatonin Receptors Are Present and Functional in Rat Caudal Artery

Masana¹,

Doolen²,

Erşahin³

et al. 2002

J Pharmacol Exp Ther

153

128

View full text Add to dashboard Cite

In rat caudal artery, contraction to melatonin results primarily from activation of MT 1 melatonin receptors; however, the role of MT 2 melatonin receptors in vascular responses is controversial. We examined and compared the expression and function of MT 2 receptors with that of MT 1 receptors in male rat caudal artery. MT 1 and MT 2 melatonin receptor mRNA was amplified by reverse transcription-polymerase chain reaction from caudal arteries of three rat strains (i.e., Fisher, Sprague-Dawley, and Wistar). Antisense (but not sense) 33 P-labeled oligonucleotide probes specific for MT 1 or MT 2 receptor mRNA hybridized to smooth muscle, as well as intimal and adventitial layers, of caudal artery. In male Fisher rat caudal artery denuded of endothelium, melatonin was 10 times more potent than 6-chloromelatonin to potentiate contraction to phenylephrine, suggesting activation of smooth muscle MT 1 melatonin receptors. The MT 1 /MT 2 competitive melatonin receptor antagonist luzindole (3 M), blocked melatonin-mediated contraction (0.1-100 nM) with an affinity constant (K B value of 157 nM) similar to that for the human MT 1 receptor. However, at melatonin concentrations above 100 nM, luzindole potentiated the contractile response, suggesting blockade of MT 2 receptors mediating vasorelaxation and/or an inverse agonist effect at MT 1 constitutively active receptors. The involvement of MT 2 receptors in vasorelaxation is supported by the finding that the competitive antagonists 4-phenyl 2-acetamidotetraline and 4-phenyl-2-propionamidotetraline, at MT 2 -selective concentrations (10 nM), significantly enhanced contractile responses to all melatonin concentrations tested (0.1 nM-10 M). We conclude that MT 2 melatonin receptors expressed in vascular smooth muscle mediate vasodilation in contrast to vascular MT 1 receptors mediating vasoconstriction.Accumulating evidence indicates that the hormone melatonin regulates vascular tone; however, the nature of the response remains controversial. Both vasoconstrictor and vasodilator responses have been reported; however, data supporting the presence of melatonin receptors is found in some, but not all, vascular beds (Mahle et al., 1997). In isolated rat caudal arteries, nanomolar concentrations of melatonin potentiate contraction induced by either endogenous or exogenous vasoconstrictors (Viswanathan et al

show abstract

Section: Discussionmentioning

confidence: 99%

“…In rat cerebral arteries and arterioles, melatonin is a direct vasoconstrictor (Geary et al, 1997;Viswanathan et al, 1997). Melatonin-mediated contraction in caudal and cerebral arteries is blocked by melatonin receptor antagonists (Viswanathan et al, 1992;Krause et al, 1995;Geary et al, 1997;Ting et al, 1997Ting et al, , 1999.…”

mentioning

confidence: 99%

MT₂Melatonin Receptors Are Present and Functional in Rat Caudal Artery

Masana¹,

Doolen²,

Erşahin³

et al. 2002

J Pharmacol Exp Ther

153

128

View full text Add to dashboard Cite

show abstract

“…We have also shown that vascular melato nin receptor expression is clearly different in spontaneously hypertensive rats (SHR), a 224 Viswanathan/Laitincn/Saavedra Vascular Melatonin Receptors model of genetic hypertension [16]. In adult SHR, melatonin receptors are not detectable in the anterior cerebral artery, and are signifi cantly lower in the tail artery when compared to age-matched Wistar-Kyoto (WKY) rats ( fig.…”

Section: Regulationmentioning

confidence: 94%

Vascular Melatonin Receptors

Viswanathan

Laitinen

Saavedra³

1993

Biological Signals

Self Cite

View full text Add to dashboard Cite

High-affinity melatonin receptors are expressed in the tail artery of the rat and arteries forming the circle of Willis of the rat and certain primates. The characteristics of the vascular melatonin receptors seem to be similar to the ones described in the central nervous system. The expression of vascular melatonin receptors in the rat is differentially regulated by factors such as strain and age, and in the female by reproductive hormones. Functional studies using the caudal artery of the rat suggest that melatonin regulates vascular tone. The highly restricted distribution of melatonin receptors in arteries involved in regulating blood flow to areas involved in heat dissipation suggests that vascular melatonin receptors may have a specific function in thermoregulatory homeostasis.

show abstract

“…Melatonin receptor density in the cerebral and caudal arteries of the rat decrease with increasing age [115], and such a decrease is pronounced in genetically hypertensive rats [116]. In the female rat, vascular melatonin receptor expression is regulated by estrogen [117].…”

Section: Melatonin Receptors In the Cardiovascular Systemmentioning

confidence: 99%

Prospects of the Clinical Utilization of Melatonin

Bubenik

Blask

Brown

et al. 1998

Biol Signals Recept

Self Cite

129

View full text Add to dashboard Cite

This review summarizes the present knowledge on melatonin in several areas on physiology and discusses various prospects of its clinical utilization. Ever increasing evidence indicates that melatonin has an immuno-hematopoietic role. In animal studies, melatonin provided protection against gram-negative septic shock, prevented stress-induced immunodepression, and restored immune function after a hemorrhagic shock. In human studies, melatonin amplified the antitumoral activity of interleukin-2. Melatonin has been proven as a powerful cytostatic drug in vitro as well as in vivo. In the human clinical field, melatonin appears to be a promising agent either as a diagnostic or prognostic marker of neoplastic diseases or as a compound used either alone or in combination with the standard cancer treatment. Utilization of melatonin for treatment of rhythm disorders, such as those manifested in jet lag, shift work or blindness, is one of the oldest and the most successful clinical application of this chemical. Low doses of melatonin applied in controlled-release preparation were very effective in improving the sleep latency, increasing the sleep efficiency and rising sleep quality scores in elderly, melatonin-deficient insomniacs. In the cardiovascular system, melatonin seems to regulate the tone of cerebral arteries; melatonin receptors in vascular beds appear to participate in the regulation of body temperature. Heat loss may be the principal mechanism in the initiation of sleepiness caused by melatonin. The role of melatonin in the development of migraine headaches is at present uncertain but more research could result in new ways of treatment. Melatonin is the major messenger of light-dependent periodicity, implicated in the seasonal reproduction of animals and pubertal development in humans. Multiple receptor sites detected in brain and gonadal tissues of birds and mammals of both sexes indicate that melatonin exerts a direct effect on the vertebrate reproductive organs. In a clinical study, melatonin has been used successfully as an effective female contraceptive with little side effects. Melatonin is one of the most powerful scavengers of free radicals. Because it easily penetrates the blood-brain barrier, this antioxidant may, in the future, be used for the treatment of Alzheimer’s and Parkinson’s diseases, stroke, nitric oxide, neurotoxicity and hyperbaric oxygen exposure. In the digestive tract, melatonin reduced the incidence and severity of gastric ulcers and prevented severe symptoms of colitis, such as mucosal lesions and diarrhea.

show abstract

Differential Expression of Melatonin Receptors in Spontaneously Hypertensive Rats

Cited by 38 publications

References 20 publications

MT₂Melatonin Receptors Are Present and Functional in Rat Caudal Artery

MT₂Melatonin Receptors Are Present and Functional in Rat Caudal Artery

Vascular Melatonin Receptors

Prospects of the Clinical Utilization of Melatonin

Contact Info

Product

Resources

About

Differential Expression of Melatonin Receptors in Spontaneously Hypertensive Rats

Cited by 38 publications

References 20 publications

MT2Melatonin Receptors Are Present and Functional in Rat Caudal Artery

MT2Melatonin Receptors Are Present and Functional in Rat Caudal Artery

Vascular Melatonin Receptors

Prospects of the Clinical Utilization of Melatonin

Contact Info

Product

Resources

About

MT₂Melatonin Receptors Are Present and Functional in Rat Caudal Artery

MT₂Melatonin Receptors Are Present and Functional in Rat Caudal Artery