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Conference Paper: Tyrosine kinase-mediated signal transduction pathway in smooth muscle activated by melatonin

TitleTyrosine kinase-mediated signal transduction pathway in smooth muscle activated by melatonin
Authors
Issue Date2000
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSG
Citation
The 1999 International Symposium on Receptor and Non-Receptor Mediated Actions of Melatonin, Hong Kong, China, 6-8 November 1999. In Biological Signals and Receptors, 2000, v. 9 n. 1, p. 59 How to Cite?
AbstractThe characteristics of melatonin receptors and mechanism of melatonin action on the quail caecum were investigated. In the crude caecal membrane preparation, saturation, kinetic and competition study revealed a single population of specific, high affinity, and low-density binding sites for 2[125I]iodomelatonin (Kd = 24.6 B 1.1 pmol/l; Bmax = 2.0 B 0.1 fmol/mg; n = 7). The biochemical and pharmacological characteristics of 2[125I]iodomelatonin binding are similar to the ML1 high-affinity melatonin receptors reported. Using the caecal ring as our study model, we showed that melatonin was able to potentiate K+ (30 mM)-induced contraction in a dose dependent manner (EC50 = 1.38 ÌM). Luzindol and 4-phenyl–2-propionamidotetraline (4-P-PDOT), two antagonists of ML1 receptor attenuated the melatonin constrictor responses with Ki = 6.4 ÌM and Ki = 3.7 ÌM, respectively. Epidermal growth factor (EGF) exerted similar potentiation as that of melatonin on the K+-predepolarized quail caecum. Genistein (40 ÌM) and erbstatin (10 Ìg/ml), two tyrosine kinases blockers, completely inhibited the contractile responses of both of the agonists studied. In contrast to melatonin and EGF, agents such as epinephrine (1 ÌM) and dibutyrylcAMP (1 mM), which are known to enhance the level of the intracellular cAMP thereby initiating protein kinase A (PKA), completely inhibited the K+-induced contraction. Moreover, an activator of protein kinase C (PKC), phorbol 12-myristate 13-acetate, failed to modify muscular responses of quail caecum to K+. The effect of melatonin in caecum rings was accompanied by an increased intracellular Ca2+ concentration ([Ca2+]i), as estimated by fura-2. The melatonin-promoted rise in [Ca2+]i, just as the K+-induced [Ca2+]I enhancement, seems to be the result of an activation of potential-dependent Ca2+ channels by both K+ and melatonin, since a specific blocker of L-type Ca2+ channels, nifedipine (1 ÌM), inhibited the contractile increments. Our results indicate that a high-affinity melatonin receptor-couple pathway of contraction is present in the quail caecum visceral smooth muscle. We also suggest that melatonin potentiates the K+-induced caecum contraction by activating ML1 receptors, which mobilize tyrosine kinases, but not PKA or PKC. The melatonin stimulation on smooth muscle may mediate through a tyrosyl phosphorylation of subunits of L-type Ca2+ channel.
Descriptionpp. 53-75 of this journal issue entitled: Receptor and Non-Receptor Mediated Actions of Melatonin - International Symposium, Hong Kong, China, November 6-8, 1999
Persistent Identifierhttp://hdl.handle.net/10722/105069
ISSN
2003 Impact Factor: 3.5

 

DC FieldValueLanguage
dc.contributor.authorKravtsov, GMen_HK
dc.contributor.authorPoon, AMSen_HK
dc.contributor.authorPang, SFen_HK
dc.date.accessioned2010-09-25T22:18:57Z-
dc.date.available2010-09-25T22:18:57Z-
dc.date.issued2000en_HK
dc.identifier.citationThe 1999 International Symposium on Receptor and Non-Receptor Mediated Actions of Melatonin, Hong Kong, China, 6-8 November 1999. In Biological Signals and Receptors, 2000, v. 9 n. 1, p. 59-
dc.identifier.issn1422-4933-
dc.identifier.urihttp://hdl.handle.net/10722/105069-
dc.descriptionpp. 53-75 of this journal issue entitled: Receptor and Non-Receptor Mediated Actions of Melatonin - International Symposium, Hong Kong, China, November 6-8, 1999-
dc.description.abstractThe characteristics of melatonin receptors and mechanism of melatonin action on the quail caecum were investigated. In the crude caecal membrane preparation, saturation, kinetic and competition study revealed a single population of specific, high affinity, and low-density binding sites for 2[125I]iodomelatonin (Kd = 24.6 B 1.1 pmol/l; Bmax = 2.0 B 0.1 fmol/mg; n = 7). The biochemical and pharmacological characteristics of 2[125I]iodomelatonin binding are similar to the ML1 high-affinity melatonin receptors reported. Using the caecal ring as our study model, we showed that melatonin was able to potentiate K+ (30 mM)-induced contraction in a dose dependent manner (EC50 = 1.38 ÌM). Luzindol and 4-phenyl–2-propionamidotetraline (4-P-PDOT), two antagonists of ML1 receptor attenuated the melatonin constrictor responses with Ki = 6.4 ÌM and Ki = 3.7 ÌM, respectively. Epidermal growth factor (EGF) exerted similar potentiation as that of melatonin on the K+-predepolarized quail caecum. Genistein (40 ÌM) and erbstatin (10 Ìg/ml), two tyrosine kinases blockers, completely inhibited the contractile responses of both of the agonists studied. In contrast to melatonin and EGF, agents such as epinephrine (1 ÌM) and dibutyrylcAMP (1 mM), which are known to enhance the level of the intracellular cAMP thereby initiating protein kinase A (PKA), completely inhibited the K+-induced contraction. Moreover, an activator of protein kinase C (PKC), phorbol 12-myristate 13-acetate, failed to modify muscular responses of quail caecum to K+. The effect of melatonin in caecum rings was accompanied by an increased intracellular Ca2+ concentration ([Ca2+]i), as estimated by fura-2. The melatonin-promoted rise in [Ca2+]i, just as the K+-induced [Ca2+]I enhancement, seems to be the result of an activation of potential-dependent Ca2+ channels by both K+ and melatonin, since a specific blocker of L-type Ca2+ channels, nifedipine (1 ÌM), inhibited the contractile increments. Our results indicate that a high-affinity melatonin receptor-couple pathway of contraction is present in the quail caecum visceral smooth muscle. We also suggest that melatonin potentiates the K+-induced caecum contraction by activating ML1 receptors, which mobilize tyrosine kinases, but not PKA or PKC. The melatonin stimulation on smooth muscle may mediate through a tyrosyl phosphorylation of subunits of L-type Ca2+ channel.-
dc.languageengen_HK
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSG-
dc.relation.ispartofBiological Signals and Receptorsen_HK
dc.rightsBiological Signals and Receptors. Copyright © S Karger AG.-
dc.titleTyrosine kinase-mediated signal transduction pathway in smooth muscle activated by melatoninen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailKravtsov, GM: gmkravts@HKUCC.hku.hken_HK
dc.identifier.emailPoon, AMS: amspoon@hkucc.hku.hken_HK
dc.identifier.emailPang, SF: hrmypsf@hkucc.hku.hken_HK
dc.identifier.authorityPoon, AMS=rp00354en_HK
dc.identifier.doi10.1159/000014623-
dc.identifier.hkuros53278en_HK
dc.identifier.volume9-
dc.identifier.issue1-
dc.identifier.spage59-
dc.identifier.epage59-
dc.publisher.placeSwitzerland-

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