Abstract
1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether AH 21-132 shares the activity of theophylline as an antagonist at adenosine A1 receptors and to assess its potency as a relaxant in intestinal smooth muscle. 2. In the transmurally-stimulated guinea-pig ileum, theophylline (1 mM), but not AH 21-132 (1 and 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM and 1 mM) of AH 21-132 themselves had a depressant effect. Neither theophylline (1 mM) nor AH 21-132 (1 and 10 microM) antagonized twitch depression induced by noradrenaline. 3. AH 21-132 (100 microM and 1 mM) depressed maximum contractions of ileum induced by both acetylcholine (ACh) and histamine. 4. In ileum treated with hyoscine (1 microM), AH 21-132 (greater than 10 microM) caused a concentration-dependent depression of the log concentration-effect curve for potassium chloride. 5. Simultaneous extracellular electrophysiological and mechanical recording from taenia caeci showed that AH 21-132 (100 microM-1 mM) inhibited spontaneous tension waves and their associated bursts of electrical spike activity. 6. Intracellular electrophysiological recording from taenia caeci showed that the mechano-inhibitory effect of 1 mM AH 21-132 was accompanied by abolition of spontaneous spike activity. Following spike abolition, the membrane potential assumed a value very close to that observed during periods of electrical quiescence prior to drug exposure. 7. AH 21-132 inhibited the activity of cyclic AMP-dependent and cyclic GMP-dependent phosphodiesterases derived from homogenates of ileal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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- AMBACHE N. Separation of the longitudinal muscle of the rabbit's ileum as a broad sheet. J Physiol. 1954 Aug 27;125(2):53–5P. [PubMed] [Google Scholar]
- Golenhoffen K., von Loh D. Elektrophysiologische Untersuchungen zur normalen Spontanaktivität der isolierten Taenia coli des Meerschweinchens. Pflugers Arch. 1970;314(4):312–328. doi: 10.1007/BF00592289. [DOI] [PubMed] [Google Scholar]
- Markstein R., Digges K., Marshall N. R., Starke K. Forskolin and the release of noradrenaline in cerebrocortical slices. Naunyn Schmiedebergs Arch Pharmacol. 1984 Jan;325(1):17–24. doi: 10.1007/BF00507049. [DOI] [PubMed] [Google Scholar]
- PATON W. D. The response of the guineapig ileum to electrical stimulation by coaxial electrodes. J Physiol. 1955 Feb 28;127(2):40–1P. [PubMed] [Google Scholar]
- Paton D. M. Structure-activity relations for presynaptic inhibition of noradrenergic and cholinergic transmission by adenosine: evidence for action on A1 receptors. J Auton Pharmacol. 1981 Sep;1(4):287–290. doi: 10.1111/j.1474-8673.1981.tb00457.x. [DOI] [PubMed] [Google Scholar]
- Sawynok J., Jhamandas K. H. Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: antagonism by theophylline. J Pharmacol Exp Ther. 1976 May;197(2):379–390. [PubMed] [Google Scholar]
- Small R. C., Boyle J. P., Cortijo J., Curtis-Prior P. B., Davies J. M., Foster R. W., Hofer P. The relaxant and spasmogenic effects of some xanthine derivatives acting on guinea-pig isolated trachealis muscle. Br J Pharmacol. 1988 Aug;94(4):1091–1100. doi: 10.1111/j.1476-5381.1988.tb11627.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Small R. C., Boyle J. P., Duty S., Elliott K. R., Foster R. W., Watt A. J. Analysis of the relaxant effects of AH 21-132 in guinea-pig isolated trachealis. Br J Pharmacol. 1989 Aug;97(4):1165–1173. doi: 10.1111/j.1476-5381.1989.tb12575.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Small R. C., Weston A. H. Simultaneous long-term recording of the mechanical and intracellular electrical activity of smooth muscles. J Pharmacol Methods. 1980 Jan;3(1):33–38. doi: 10.1016/0160-5402(80)90062-5. [DOI] [PubMed] [Google Scholar]
- Small R. C., Weston A. H. Simultaneous recording of electrical and mechanical activity from intestinal and vascular smooth muscle [proceedings]. Br J Pharmacol. 1977 Nov;61(3):491P–492P. [PMC free article] [PubMed] [Google Scholar]
- Torphy T. J. Action of mediators on airway smooth muscle: functional antagonism as a mechanism for bronchodilator drugs. Agents Actions Suppl. 1988;23:37–53. doi: 10.1007/978-3-0348-9156-1_2. [DOI] [PubMed] [Google Scholar]