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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hutchinson, D. S. Summers, R. J. Evans, B. A. |
| Description | Author Affiliation: Hutchinson DS ( Department of Pharmacology, Monash University, Victoria, Australia 3800.) |
| Abstract | 1. This study examines beta(1)-, beta(2)- and beta(3)-adrenoceptor (AR)-mediated responses, mRNA levels and radioligand binding in ileum from beta(3)-AR knock-out (-/-) (KO) and wild type (+/+) (FVB) mice. 2. In KO and FVB mice, SR59230A (100 nM) (beta(3)-AR antagonist) antagonized responses to (-)-isoprenaline in both KO and FVB mice. (-)-Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 nM) (beta(2)-AR antagonist). Responses to (-)-isoprenaline were more strongly antagonized by CGP20712A (100 nM) (beta(1)-AR antagonist), propranolol (1 microM) (beta(1)-/beta(2)-AR antagonist), carvedilol (100 nM) (non-specific beta-AR antagonist), and CGP12177A (100 nM) (beta(1)-/beta(2)-AR antagonist) in ileum from KO than in FVB mice. 3. Responses to CL316243 (beta(3)-AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 nM) but not by propranolol (1 microM) or carvedilol (100 nM). CL316243 was ineffective in relaxing ileum from KO mice. 4. CGP12177A had no agonist actions in ileum from either KO or FVB mice. 5. beta(1)-AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of beta(1)-/beta(2)-AR binding sites (B(max)). beta(2)-AR mRNA levels were unaffected while no beta(3)-AR mRNA was detected in KO mice. 6. In mouse ileum, beta(3)-ARs and to a lesser extent beta(1)-ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice beta(1)-ARs functionally compensate for the lack of beta(3)-ARs, and this is associated with increased beta(1)-AR mRNA and levels of binding. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 132 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2001-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Ileum Drug Effects Pindolol Analogs & Derivatives Receptors, Adrenergic, Beta-1 Receptors, Adrenergic, Beta-3 Genetics Adrenergic Beta-Agonists Pharmacology Adrenergic Beta-Antagonists Animals Dioxoles Genotype In Vitro Techniques Isoproterenol Mice Mice, Knockout Muscle Relaxation Muscle, Smooth Propranolol RNA, Messenger Biosynthesis Metabolism Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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