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Intraglandularly administered ETs failed to elicit salivation per se. However, ET-1, but not ET-3, potentiated both cholinergic- and adrenergic-evoked salivation through ET<jats:sub>A<\/jats:sub>receptors. ET-1 decreased cAMP content but increased phosphoinositide hydrolysis, whereas ET-3 attenuated both intracellular pathways. The expression of ET<jats:sub>A<\/jats:sub>and ET<jats:sub>B<\/jats:sub>receptor mRNAs as well as that of ETs was revealed in the submandibular gland by RT-PCR. Immunohistochemical studies showed that ET<jats:sub>A<\/jats:sub>receptor staining was localized around the interlobular ducts and acini, compatible with the myoepithelial cells' location, whereas ET<jats:sub>B<\/jats:sub>receptor staining was restricted to small blood vessels. When applied to the brain, both ETs induced no salivation but enhanced cholinergic- and adrenergic-evoked salivary secretion through parasympathetic pathways. ET-1 response was mediated by brain ET<jats:sub>A<\/jats:sub>receptors, whereas that of ET-3 was presumably through nonconventional ET receptors. Present findings show that ETs are involved in the brain regulation of cholinergic- and adrenergic-stimulated submandibular gland secretion through the activation of distinct brain ET receptors and parasympathetic pathways. However, when ETs were administered into the gland, only ET-1 enhanced cholinergic and adrenergic salivation likely through myopithelial cell contraction by activating ET<jats:sub>A<\/jats:sub>receptors coupled to phospholipase C. The presence of ETs and ET receptors suggests the existence of an endothelinergic system in the submandibular gland.<\/jats:p>","DOI":"10.1152\/ajpregu.00041.2010","type":"journal-article","created":{"date-parts":[[2010,10,14]],"date-time":"2010-10-14T07:13:31Z","timestamp":1287040411000},"page":"R109-R120","source":"Crossref","is-referenced-by-count":6,"title":["Endothelins participate in the central and peripheral regulation of submandibular gland secretion in the rat"],"prefix":"10.1152","volume":"300","author":[{"given":"Maria S.","family":"Ventimiglia","sequence":"first","affiliation":[{"name":"C\u00e1tedras de Fisiopatolog\u00eda,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myrian R.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"C\u00e1tedras de Fisiopatolog\u00eda,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanina 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