Reduction of regional cerebral blood flow by melatonin in young rats

Capsoni, Simona; Stankov, Bojidar; Fraschini, F.

doi:10.1097/00001756-199506090-00029

Cited by 56 publications

(34 citation statements)

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“…Indeed, a functional role for melatonin binding sites and receptors was established by studies demonstrating that melatonin causes vasoconstriction in certain vascular beds and vasodilation in others. For example, melatonin causes direct vasoconstriction of cerebral arteries (Capsoni et al, 1995;Geary et al, 1997;Viswanathan et al, 1997) and vasodilation in caudal arteries (Doolen et al, 1998;Masana et al, 2002) in rats.…”

Section: Discussionmentioning

confidence: 99%

MT₂ Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

Tunstall

Shukla²,

Grazul-Bilska³

et al. 2010

J Pharmacol Exp Ther

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Previous studies from our laboratory demonstrated that melatonin inhibits nitric oxide (NO)-induced relaxation in porcine coronary arteries. The present study was designed to further characterize the mechanisms underlying this inhibitory effect of melatonin. Western immunoblot studies identified the presence of melatonin type 2 (MT 2 ) receptors, but not MT 1 or MT 3 receptors, in porcine coronary arteries. Immunohistochemical analysis revealed that MT 2 receptors colocalized with ␣-actin in the smooth muscle cell layer. In coronary arterial rings suspended in organ chambers for isometric tension recording, melatonin (10 Ϫ7 M) inhibited relaxations induced by the exogenous NO donor sodium nitroprusside (SNP; 10 Ϫ9 to 10 Ϫ5 M) and by the ␣ 2 -adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline (UK14,304; 10 Ϫ9 to 10 Ϫ5 M), an endothelium-dependent vasodilator. The inhibitory effect of melatonin on SNP-and UK14,304-induced relaxations was abolished in the presence of the selective MT 2 receptor antagonists 4-phenyl-2-propionamidotetralin (4P-PDOT; 10 Ϫ7 M) and luzindole (10 Ϫ7 M). In contrast to melatonin, the selective MT 3 receptor agonist 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT; 10 Ϫ7 M) had no effect on the concentrationresponse curves to either SNP or UK14,304. Melatonin (10 Ϫ7 M) had no effect on coronary artery relaxation induced by 8-bromoguanosine 3Ј,5Ј-cyclic monophosphate, but it significantly attenuated the increase in intracellular cyclic GMP levels in response to SNP (10 Ϫ5 M). This effect of melatonin was abolished in the presence of 4P-PDOT (10 Ϫ7 M). Taken together, these data support the view that melatonin acts on MT 2 receptors in coronary vascular smooth muscle cells to inhibit NO-induced increases in cyclic GMP and coronary arterial relaxation, thus demonstrating a novel function for MT 2 receptors in the vasculature.

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Section: Discussionmentioning

confidence: 99%

MT₂ Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

Tunstall

Shukla²,

Grazul-Bilska³

et al. 2010

J Pharmacol Exp Ther

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“…As melatonin receptors were detected in cerebral arteries [110], melatonin administration reduced blood pressure in rats [132] and in hypertensive humans [133], and as melatonin was reported to relax smooth muscles of arteries [134] including the basilar artery [135], it could be hypothesized that an alteration in cerebral blood flow induced by melatonin may have a beneficial effect on the development of migraine headaches. However, as a reduction in cerebral blood flow was also reported [136] and controversy remains whether migraine is of vascular or neuronal origin or whether migraine is induced by the reduction or an increase in blood flow to certain brain areas, only large …”

Section: Can Melatonin Be a New Treatment For Migraine Headaches?mentioning

confidence: 99%

Prospects of the Clinical Utilization of Melatonin

Bubenik

Blask

Brown

et al. 1998

Biol Signals Recept

129

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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.

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“…The localization of these binding sites is discrete (there is no evidence for similar binding sites on either coronary artery, carotid artery or aorta of the rat) and this has been taken as evidence for a thermoregulatory role of the pineal hormone (Viswanathan et al, 1990;Saarela & Reiter, 1993). In support of this proposal, near physiological levels of melatonin (0.3 nM to 1 nM) have been reported to increase vascular tone in both isolated cerebral vessels (Geary et al, 1995;Mahle et al, 1995), the cerebral vascular bed (Capsoni et al, 1995) and the isolated tail artery (Evans et al, 1992). However, the precise nature of the vasoconstriction appears to be a function of the recording technique employed.…”

Section: Introductionmentioning

confidence: 99%

Studies on the vasoconstrictor action of melatonin and putative melatonin receptor ligands in the tail artery of juvenile Wistar rats

Ting

Dunn

Davies³

et al. 1997

British J Pharmacology

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1 In this study we compared the vasoconstrictor activity of melatonin in rat isolated tail artery using two dierent recording systems, the Halpern pressure myograph and the Halpern-Mulvany wire myograph, with the view to determining a reliable method for obtaining pharmacological data on vascular melatonin receptors. In addition, we characterized the melatonin receptor in this preparation, using analogues of melatonin, and examined the activity of various naphthalenic derivatives with biological activity in non-vascular models of melatonin receptors. 2 Using the Halpern pressure myograph, cumulative addition of melatonin (0.1 nM to 1 mM) produced direct vasoconstriction (19.3+6.4% reduction in lumen diameter, n=5) in ®ve of 11 pressurized segments, with pEC 50 of 9.14+0.17. Similarly, non-cumulative application of melatonin caused vasoconstriction (19.7+4.6% reduction in lumen diameter, n=7) in seven of 20 preparations examined with pEC 50 of 8.74+0.26. The selective alpha 2 -adrenoceptor agonist, UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate), produced vasoconstriction in all`melatonin-insensitive' preparations.3 Melatonin (0.1 nM to 1 mM) failed to elicit isometric contractions of tail artery segments in the Halpern wire myograph, but produced concentration-dependent potentiation of electrically-evoked, isometric contractions (maximum eect of 150 ± 200% enhancement) when applied either noncumulatively (seven of seven preparations) or cumulatively (four of seven preparations). The pEC 50 value of melatonin (non-cumulative) was 8.50+0.10 (n=7) which was not dierent from that obtained in the pressure myograph. All further experiments were conducted using a non-cumulative protocol against electrically-evoked, isometric contractions. 4 Based on the pEC 50 values for the melatonin analogues examined, the pharmacological pro®le for the enhancement of electrically-evoked contractions was 2-iodomelatonin46-chloromelatonin5(7)-AMMTC 5 S216345melatonin5S200984S202425S2030446-hydroxymelatonin4S209324 (+) -AM-MTC4N-acetyl-5-HT. Our data suggests the vascular receptor belongs to the MEL 1 -like subtype. All the indole-based analogues of melatonin, 2-iodomelatonin, (7)-AMMTC, (+)-AMMTC, S20932, 6-chloromelatonin, 6-hydroxymelatonin and N-acetyl-5-HT, behaved as full agonists. All the naphthalenic derivatives examined, S21634, S20098, S20242 and S20304 behaved as partial agonists relative to melatonin. 5 The naphthalenic-based antagonists, S20928 and S20929, did not modify electrically-evoked, isometric contractions of the tail artery, but produced a parallel, rightward displacement of the melatonin concentration-response curve. Based upon the eect of 1 mM S20928 and S20929, the estimated pK B values for these antagonists were 7.18+0.25 (n=4) and 7.17+0.25 (n=5), respectively. 6 We demonstrated that enhancement of electrically-evoked, isometric contractions of the rat isolated tail artery (using the Halpern-Mulvany wire myograph) is a simple and reproducible model for assessing the activity of putative a...

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Reduction of regional cerebral blood flow by melatonin in young rats

Cited by 56 publications

References 0 publications

MT₂ Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

MT₂ Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

Prospects of the Clinical Utilization of Melatonin

Studies on the vasoconstrictor action of melatonin and putative melatonin receptor ligands in the tail artery of juvenile Wistar rats

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Reduction of regional cerebral blood flow by melatonin in young rats

Cited by 56 publications

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MT2 Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

MT2 Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

Prospects of the Clinical Utilization of Melatonin

Studies on the vasoconstrictor action of melatonin and putative melatonin receptor ligands in the tail artery of juvenile Wistar rats

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MT₂ Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries

MT₂ Receptors Mediate the Inhibitory Effects of Melatonin on Nitric Oxide-Induced Relaxation of Porcine Isolated Coronary Arteries