Abstract
The present study was undertaken to look for the effect of chloroethylclonidine (CEC) on prejunctional alpha-2 autoreceptors of the canine saphenous vein. The effect was tested on tritium overflow evoked by electrical stimulation from tissues preloaded with 0.2 μM 3H-norepinephrine. Yohimbine (3–300 nM) and CEC (1–125 μM) increased and UK-14,304 reduced the overflow of tritium evoked by 300 pulses (1 Hz). The maximal increase of tritium overflow caused by yohimbine was much higher than that caused by CEC: 3.82 and 1.74 times, respectively. CEC (5 μM) abolished both the inhibition caused by UK-14,304 and the enhancement of tritium overflow caused by yohimbine. However, when CEC was added after yohimbine, it reduced the electrically evoked overflow of tritium, the maximal effect being a reduction of tritium overflow by 35%. Prazosin (1–100 nM) did not change either the inhibitory effect of UK-14,304 or the facilitatory effect of CEC. These results suggest that CEC acts on two different subtypes of prejunctionalalpha-2 autoreceptors; on one of them it acts as an antagonist and increases the electrically evoked overflow of tritium (and inhibits both the effect of UK-14,304 and yohimbine); on the other it acts as an agonist and reduces the electrically evoked overflow of tritium. Alternatively, one can admit that CEC is able to inhibitalpha-2 autoreceptors, which causes an increase of the transmitter release, and to activate a nonadrenergic inhibitory receptor thus causing a reduction of the transmitter release.
Footnotes
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Send reprint requests to: S. Guimarães, Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-Porto, Portugal.
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↵1 This work was supported by Junta Nacional de Investigação Cientı́fica e Tecnológica (JNICT)-Project number PECS/P/SAU/80/95, by PRAXIS/2/2.1/SAU/1293/95 and by Biomed 2 (EureCa project).
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↵2 Present address: Departamento de Farmacologia. I.B. Botucatu-UNESP, 18600 Botucatu, SP, Brasil.
- Abbreviations:
- CEC
- chloroethylclonidine
- U-0521
- 3,4-dihydroxy-2-methylpropiophenone
- Received December 31, 1996.
- Accepted May 23, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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