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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mccrea, K. E. Hill, S. J. |
| Description | Author Affiliation: McCrea KE ( Department of Physiology & Pharmacology, Medical School, Queen's Medical Centre, Nottingham.) |
| Abstract | 1. The accumulation of cyclic AMP stimulated by salmeterol, a long-acting beta 2-adrenoceptor agonist and by isoprenaline, a non-selective beta-adrenoceptor agonist have been compared in the B50 neuroblastoma cell line. 2. Salmeterol produced a concentration-dependent increase in the accumulation of total [3H]-cyclic AMP in B50 cells yielding an EC50 value of 37 nM which was lower than that obtained with isoprenaline (294 nM). The maximum response to salmeterol was only 46% of that obtained with isoprenaline. 3. The beta 2-adrenoceptor antagonist, ICI 118551, inhibited the responses to both salmeterol (apparent KD 2.2 nM) and isoprenaline (apparent KD 1.6 nM). However, the beta 1-adrenoceptor antagonist, atenolol, produced no significant effect at concentrations up to 100 microM. 4. Salmeterol (1 microM) changed the concentration-response curve of isoprenaline in the manner of a partial agonist interacting with a full agonist. The KD of salmeterol obtained from the interaction was 55.6 nM. 5. Whereas salmeterol has a slow onset of action in airway smooth muscle compared to other beta 2-adrenoceptor agonists, in B50 monolayers both salmeterol and isoprenaline produced a rapid increase in cyclic AMP accumulation (t1/2 1.1 min and 0.4 min respectively). 6. Despite the existence of cyclic AMP efflux mechanisms that exist in this cell line it was possible to investigate the duration of agonist action by measuring intracellular levels of the second messenger. Replacement of drug-containing medium with fresh buffer led to a rapid reduction in intracellular levels of cyclic AMP in isoprenaline-stimulated cells whereas cyclic AMP accumulation was sustained for much longer periods in salmeterol-stimulated cells. However, the persistent action of salmeterol could be reversed by the addition of a beta2-selective antagonist.7. These results confirm that salmeterol has a high affinity, but low efficacy (relative to isoprenaline) for beta2-adrenoceptors coupled to cyclic AMP accumulation and that the drug persists at its site of action for long periods in the B50 neuronal cell line. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 110 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1993-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Beta-Agonists Pharmacology Albuterol Analogs & Derivatives Cyclic AMP Metabolism Neurons Receptors, Adrenergic, Beta-2 Drug Effects Animals Central Nervous System Neoplasms Isoproterenol Neuroblastoma Salmeterol Xinafoate Tumor Cells, Cultured Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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