title: Alpha-adrenoceptor-mediated prejunctional effects of chloroethylclonidine in the canine saphenous vein.
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 microM 3H-norepinephrine. Yohimbine (3-300 nM) and CEC (1-125 microM) 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 microM) 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 prejunctional alpha-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 inhibit alpha-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.
authors.affiliation: Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Guimarães
authors.forename: M Q
authors.initials: MQ
authors.lastname: Paiva
authors.forename: O
authors.initials: O
authors.lastname: Pereira
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D017660:Autoreceptors; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C051731:chlorethylclonidine; D000068438:Brimonidine Tartrate; D003000:Clonidine; D011224:Prazosin