Yoshiki Iwabuchi

Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A-343 in rat salivary glands: Identification of a potential therapeutic agent for treatment of Sjörgen's syndrome

1. We examined the sialogogic activities in rat major salivary glands of SNI-2011, in comparison with those of pilocarpine and McN-A-343, and we characterized the subtypes of muscarine receptors that are involved in the sialogogic responses to SNI-2011 and McN-A-343. 2. SNI-2011 at doses ranging from 1 to 10 mg/kg (i.v.) increased the secretion of saliva in a dose-dependent manner. The dose-response curves for SNI-2011 were approximately parallel to curves for pilocarpine but the potency of SNI-2011 was about 25-fold lower than that of pilocarpine. 3. The total volume of saliva secreted in response to McN-A-343 was very much less than that secreted in response to SNI-2011. 4. The salivation induced by SNI-2011 and by McN-A-343 was inhibited by various antagonists with the following rank order of potency: 4-DAMP >> pirenzepine >> AF-DX 116. 5. Our results suggest that the sialogogic effects of SNI-2011 and McN-A-343 are mediated by direct stimulation of M3 receptors in salivary glands and that SNI-2011 may prove useful in the management of xerostomia in patients with Sjögrens syndrome.

Effects of vasoactive intestinal peptide and its homologues on the acetylcholine-mediated secretion of fluid and protein from the rat submandibular gland

1. Acetylcholine-mediated (ACh-mediated) secretion of fluid and protein from rat submandibular glands was enhanced by intravenous injection of vasoactive intestinal peptide (VIP) and of secretin but not of peptide histidine isoleucine (PHI) or gastric inhibitory peptide (GIP). 2. When VIP and ACh were administered together, the enhancement of fluid secretion was inhibited by pretreatment with atropine or 4-DAMP and the enhancement of protein secretion was inhibited by pretreatment with atropine or phentolamine. 3. The enhancement of the ACh-induced secretion of fluid by secretin was strongly inhibited by pretreatment with atropine, and it was weakly inhibited by pretreatment with phentolamine or haloperidol. 4. These results suggest that the synergistic effects of VIP, PHI, secretin and GIP on the ACh-mediated secretion of fluid and protein from the rat submandibular gland do not reflect the extent of the structural homology of each peptide to VIP.

Effects of calcitonin and calcitonin gene-related peptide on the substance P-mediated secretion of fluid from the rat submandibular gland.

1. The effects of rat calcitonin gene-related peptide (rCGRP), rat calcitonin (rCT) and salmon calcitonin (sCT) on the substance P-mediated (SP-mediated) secretion of fluid from the rat submandibular gland were investigated. 2. Rat CGRP potentiated and prolonged the SP-mediated secretion of fluid from the rat submandibular gland in a dose-dependent manner. CGRP also enhanced methacholine- and phenylephrine-mediated secretion of fluid. 3. The potentiating effect of the combination of rCGRP and SP was somewhat reduced by pretreatment with spantide, human CGRP8-37 and atropine but not by pretreatment with phentolamine or with propranolol. 4. Salmon CT at a low dose mimicked the effect of rCGRP on the SP-mediated secretion of fluid, but its potency was lower than that of rCGRP. However, rCT had no effect on the SP-mediated secretion of fluid. 5. These results suggest that the potentiating effects of rCGRP and SP might involve cholinergic receptors, as well as CGRP and tachykinin receptors, and that sCT, but not rCT, is able to mimic rCGRP in potentiating the secretion of fluid induced by SP.

Interaction Between Substance P and β‐Adrenergic Agonists in the Modulation of the Secretion of Fluid and Protein by the Rat Submandibular Gland

The interactions between substance P and β‐adrenergic agonists such as isoprenaline, dobutamine and terbutaline in the control of the secretion of fluid and protein from the rat submandibular gland have been examined.