Effects of pilocarpine and cevimeline on Ca2+ mobilization in rat parotid acini and ducts.
Previous reports suggested that there is no significant difference in the binding affinity of pilocarpine and cevimeline on muscarinic receptors (1). However, in vivo studies from our laboratory suggested that pilocarpine-induced salivation from the parotid gland is greater than that induced by cevimeline in rats. Therefore, in the present study, sialogogue-induced intracellular Ca(2+) mobilization was investigated in isolated parotid gland cells in vitro. Pilocarpine and cevimeline increased the intracellular Ca(2+) concentration of parotid gland acinar and duct cells over 1 microM in a dose-dependent manner. Pilocarpine-induced responses were higher than cevimeline-induced responses. Ca(2+) responses to both agents were completely blocked by 1 microM 4-DAMP, an M3 muscarinic receptor antagonist. In the absence of extracellular Ca(2+), both sialogogues induced transient Ca(2+) increase in parotid gland acinar cells. These results suggest that the sialogogues stimulate some common routes via the Ca(2+) signaling in parotid gland acinar cells. We also report a significant difference of Ca(2+) responses in concentration between pilocarpine and cevimeline in parotid gland acinar cells. The different Ca(2+) responses between the sialogogues would explain the different saliva volumes from the parotid gland between them that we have observed in previous in vivo studies.
Department of Biosciences, Kyushu Dental College, Kitakyushu, Japan.
Kentaro
K
Ono
Tomohiro
T
Inagaki
Taichi
T
Iida
Ryuji
R
Hosokawa
Kiyotoshi
K
Inenaga
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D013876:Thiophenes; D010862:Pilocarpine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C059240:cevimeline; D002118:Calcium