Source:http://linkedlifedata.com/resource/pubmed/id/11679205
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2001-10-26
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| pubmed:abstractText |
KMCP-98 is a newly synthesized adenosine receptor agonist by alkylation at the 7-position of the xanthines nucleus. We first investigated the pharmacological activities of KMCP-98 under in vivo and in vitro conditions. Acute intravenous injection of KMCP-98 (1.0, 2.0 and 3.0 mg/kg) produced a temporary fall in blood pressure and heart rate, followed by a sustained fall in heart rate in pentobarbital-anesthetized Wistar rats. The hypotensive and bradycardiac responses were inhibited by pretreatment with an A(1) adenosine receptor antagonist 8-phenyltheophylline (8-PT, 0.5 mg/kg). Both KMCP-98 and adenosine (0.3-100 microM) produced negative inotropic activity in isolated guinea pig left atria. The negative inotropic activity of KMCP-98 was significantly blocked by pretreatment with A(1) receptor antagonists 8-PT (10 microM) and xanthine amine congener (XAC, 10 microM), a nonselective adenosine antagonist theophylline (10 microM), a K(+) channel blocker tetraethylammonium (TEA, 10 mM) and a K(ATP) channel blocker glibenclamide (1 microM). KMCP-98 (0.03-30 microM) produced concentration-dependent relaxations in carbachol (1 microM) precontracted guinea pig tracheal smooth muscle. The trachea relaxant response of KMCP-98 was markedly inhibited by A(2), A(2a) and A(2b) adenosine receptor antagonists 3,7-dimethyl-1-propargylxanthine (DMPX, 10 microM), 8-(3-chlorostyryl)caffeine (CSC, 10 microM) and alloxazine (10 microM), respectively, the nitric oxide synthase (NOS) inhibitor L-NAME (100 microM) and also by TEA and glibenclamide. In addition, KMCP-98 (0.03-30 microM) elicited relaxant response in norepinephrine (3 microM) precontracted rat thoracic aorta in a concentration-dependent manner. The thoracic aorta relaxant response of KMCP-98 was also significantly inhibited by DMPX, CSC, alloxazine, L-NAME, TEA and glibenclamide. Furthermore, the binding characteristics of KMCP-98, adenosine and 5'-N-ethylcarboxaminoadenosine (NECA) were evaluated in [(3)H]DPCPX and [(3)H]CGS 21680 binding to rat cortex and striatum, respectively. The K(i) values of KMCP-98 for predominate A(1) and A(2) adenosine receptor sites were 3908+/-952 and 158+/-10 nM, respectively. In conclusion, KMCP-98 was found to be a xanthine-based adenosine receptor agonist associated cardiac depression, tracheal and aortic smooth muscle relaxations.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/Purinergic P1 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P1,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Xanthines
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0306-3623
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
35
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
47-57
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:11679205-Animals,
pubmed-meshheading:11679205-Blood Pressure,
pubmed-meshheading:11679205-Carbachol,
pubmed-meshheading:11679205-Electric Stimulation,
pubmed-meshheading:11679205-Female,
pubmed-meshheading:11679205-Guinea Pigs,
pubmed-meshheading:11679205-Heart Atria,
pubmed-meshheading:11679205-Heart Rate,
pubmed-meshheading:11679205-Male,
pubmed-meshheading:11679205-Models, Animal,
pubmed-meshheading:11679205-Models, Cardiovascular,
pubmed-meshheading:11679205-Muscle, Smooth, Vascular,
pubmed-meshheading:11679205-Muscle Relaxation,
pubmed-meshheading:11679205-Purinergic P1 Receptor Agonists,
pubmed-meshheading:11679205-Radioligand Assay,
pubmed-meshheading:11679205-Rats,
pubmed-meshheading:11679205-Rats, Wistar,
pubmed-meshheading:11679205-Receptors, Purinergic P1,
pubmed-meshheading:11679205-Trachea,
pubmed-meshheading:11679205-Vasodilator Agents,
pubmed-meshheading:11679205-Xanthines
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| pubmed:year |
2000
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| pubmed:articleTitle |
A unique xanthine derivative KMCP-98 with activation of adenosine receptor subtypes.
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| pubmed:affiliation |
Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shin-Chuan 1st Road, Kaohsiung 807, Taiwan.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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