Receptores de la serotonina que inhiben el tono simpático vasopresor en la rata descerebrada y desmedulada

La serotonina (5-hidroxitriptamina; 5-HT), produce simpatoinhibición vascular mediante la activación de receptores 5-HT1 presinápticos. Después de considerar los mecanismos de modulación de la unión neuroefectora, la presente revisión analiza los hallazgos que identifican el perfil farmacológico de los receptores serotoninérgicos que inhiben las respuestas vasopresoras simpáticas en la rata descerebrada y desmedulada. En este sentido, se ha demostrado que la impatoinhibición inducida por la 5-HT: (i) no se modifica después de administrar solución salina o los antagonistas selectivos ritanserina (5-HT2), MDL72222 (5-HT3) o tropisetrón (5-HT3/4); (ii) es antagonizada por la metisergida, un antagonista no selectivo de los receptores 5-HT1 y 5-HT2; en tanto que (iii) la 5-carboxamidotriptamina (5-CT), un agonista no selectivo del receptor 5-HT1, produce un efecto mimético potente, así como los agonistas selectivos 8-OH-DPAT (5-HT1A), indorrenato (5-HT1A), CP93,129 (5-HT1B) y sumatriptán (5-HT1B/1D). Estos hallazgos demuestran la participación de los receptores simpatoinhibitorios 5-HT1. Con el uso de antagonistas selectivos, en estudios subsecuentes se demostró que la simpatoinhibición producida por el indorrenato, CP93,129 y sumatriptán fue antagonizada en forma selectiva por, respectivamente, el WAY100635 (5-HT1A), cianopindolol (5-HT1A/1B) y GR127935 (5-HT1B/1D). Estos resultados indican que, en la vasculatura sistémica de la rata, los receptores simpatoinhibitorios 5-HT1 correlacionan con los subtipos 5-HT1A, 5-HT1B y 5-HT1D.

serotonin (5-hydroxytryptamine; 5-HT) has been shown to produce vascular sympatho-inhibition in a wide variety of isolated blood vessels by activation of prejunctional 5-HT1 receptors. After considering the mechanisms involved in modulating neuroeffector transmission, the present review analyzes the experimental findings identifying the pharmacological profile of the 5-HT receptors that inhibit the sympathetically-induced vasopressor responses in pithed rats. Thus, 5-HT-induced sympatho-inhibition has been shown to be: (i) unaffected by physiological saline or by the selective antagonists ritanserin (5-HT2), MDL72222 (5-HT3) or tropisetron (5-HT3/4); (ii) blocked by methysergide, a non-selective 5-HT1/2 receptor antagonist; and (iii) potently mimicked by 5-carboxamidotryptamine (5-CT), a non-selective 5-HT1 receptor agonist, as well as by the selective agonists 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP93,129 (5-HT1B), and sumatriptan (5-HT1B/1D). These findings show the involvement of prejunctional 5-HT1 receptors. With the use of selective antagonists, it has been shown subsequently that the sympathoinhibition induced by indorenate, CP93,129, and sumatriptan was selectively antagonized by WAY100635 (5-HT1A), cyanopindolol (5-HT1A/1B), and GR127935 (5-HT1B/1D), respectively. These results demonstrate that the 5-HT1 receptors mediating sympatho-inhibition on the systemic vasculature of pithed rats resemble the pharmacological profile of the 5-HT1A, 5-HT1B, and 5-HT1D subtypes.