Open AccessRestoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice
Author(s) -
Igor Santana de Melo,
Návylla Candeia-Medeiros,
Jaqueline dos Santos Ferro,
Polliane Maria Cavalcante-Araújo,
Tales Lyra de Oliveira,
Cássio Eráclito Alves dos Santos,
Léia Cardoso-Sousa,
Emília Maria Gomes Aguiar,
Stephanie Wutke Oliveira,
Olagide Wagner de Castro,
Renata Pereira Alves-Balvedi,
Luciano Pereira Rodrigues,
Jandir M. Hickmann,
Douglas Alexsander Alves,
Igor Andrade Santos,
Ana Carolina Gomes Jardim,
Walter L. Siqueira,
Angelo Ricardo Fávaro Pipi,
Luíz Ricardo Goulart,
Emiliano Barreto,
Robinson SabinoSilva
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0229761
Subject(s) - opioid , (+) naloxone , opioid receptor , chemistry , pharmacology , nociception , receptor , morphine , saliva , salivary gland , submandibular gland , endocrinology , medicine , biology , biochemistry
Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm -1 ; Amide II, 1594-1494cm -1 ; CH 2 /CH 3 , 1488-1433cm -1 ; C = O, 1432-1365cm -1 ; PO 2 asymmetric, 1290-1185cm -1 ; PO 2 symmetric, 1135-999cm -1 ) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.