Pharmacological evidence that 5-HT1A/1B/1D, α2-adrenoceptors and D2-like receptors mediate ergotamine-induced inhibition of the vasopressor sympathetic outflow in pithed rats.
Eur J Pharmacol
; 740: 512-21, 2014 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-24975101
ABSTRACT
The sympathetic nervous system that innervates the peripheral circulation is regulated by several mechanisms/receptors. It has been reported that prejunctional 5-HT1A, 5-HT1B, 5-HT1D, D2-like receptors and α2-adrenoceptors mediate the inhibition of the vasopressor sympathetic outflow in pithed rats. In addition, ergotamine, an antimigraine drug, displays affinity at the above receptors and may explain some of its adverse/therapeutic effects. Thus, the aims of this study were to investigate in pithed rats (i) whether ergotamine produces inhibition of the vasopressor sympathetic outflow; and (ii) the major receptors involved in this effect. For this purpose, male Wistar pithed rats were pre-treated with gallamine (25 mg/kg; i.v.) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9; 0.03-3 Hz) or to receive i.v. bolus of exogenous noradrenaline (0.03-3 µg/kg). I.v. continuous infusions of ergotamine (1 and 1.8 µg/kgmin) dose-dependently inhibited the vasopressor responses to sympathetic stimulation but not those to exogenous noradrenaline. The sympatho-inhibition elicited by 1.8 µg/kg min ergotamine was (i) unaffected by saline (1 ml/kg); (ii) partially antagonised by WAY 100635 (5-HT1A; 30 µg/kg) and rauwolscine (α2-adrenoceptor; 300 µg/kg), and (iii) dose-dependently blocked by GR 127935 (5-HT1B/1D; 100 and 300 µg/kg) or raclopride (D2-like; 300 and 1000 µg/kg), The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. The above results suggest that ergotamine induces inhibition of the vasopressor sympathetic outflow by activation of prejunctional 5-HT1A, 5-HT1B/1D, α2-adrenoceptors and D2-like receptors in pithed rats.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Dopamina D2
/
Receptores Adrenérgicos alfa 2
/
Receptores 5-HT1 de Serotonina
/
Ergotamina
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2014
Tipo de documento:
Article
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS