Lowered Susceptibility of Muscarinic Receptor Involved in Salivary Secretion of Streptozotocin-Induced Diabetic Rats

Abstract

ABSTRACT-We investigated the responses of salivary secretion and the susceptibility of the muscarinic receptors in the salivary glands of the streptozotocin (STZ)-induced diabetic rats (STZ rats). Giving water ad libitum, the amount of whole saliva with no stimulation was similar in the STZ and the control rats. Pilocarpine increased salivary secretion in both groups, although the effect in the STZ rats was two to three fold less than in the control rats. If the animals were restricted from taking water for 6 h, salivary secretion was not slightly changed in the STZ rats in spite of a remarkable increase in the control. An obvious decrease in salivary secretion of the STZ rats was negatively correlated with an increase in urination. Furthermore, salivary secretion from the parotid gland was increased in a dose-dependent manner with pilocarpine in the control rats, but not in the STZ rats. In the [3 H]quinuclidinyl benzilate (QNB) binding studies for muscarinic receptor of the STZ rats, Bmax was decreased in the parotid gland and Kd was increased in the submandibular gland. Competitive inhibition of [3 H]QNB binding to both glands showed an increase in IC50 of pilocarpine and carbachol. These results suggest that a decrease in salivary secretion of STZ rats is not only induced by a water loss, but also closely associated with the lowered susceptibility of the muscarinic receptors.

Stereology and ultrastructure of the salivary glands of diabetic Nod mice submitted to long‐term insulin treatment

“…Differences in the tissue responses between parotid and submandibular glands have already been reported for chemically induced diabetic rats, mainly in terms of parotid gland weight, which did not show significant alterations (Anderson and Johnson, 1981). Also, chemically induced diabetic rats submitted to glycemic control for a period of 1 hr to 7 days demonstrated recovery of salivary secretion levels and a decline in the accumulation of lipid droplets in the cytoplasm of parotid and submandibular salivary glands (Anderson, 1983;Morris et al, 1992;Watanabe et al, 2001). However, the authors emphasized that this treatment does not reflect total recovery of glandular function or morphology.…”

“…On the other hand, an increase in protein synthesis in the submandibular glands has been observed in chemically induced diabetic rats after they had received a single dose of insulin. However, the authors did not characterize both functional and morphological recovery of the glands (Anderson and Shapiro, 1980;Watanabe et al, 2001). Also, no significant recovery of parotid gland weight was observed in other studies administering a single dose of insulin to chemically induced diabetic rats (Anderson, 1987;Pinkstaff, 1996).…”

“…This type of diabetes results from absolute insulin deficiency caused by the autoimmune destruction of ␤-cells (Hamilton and Blackwood, 1977). The relationship between diabetes mellitus and both cellular alterations and changes in salivary components has been studied in experimental and clinical investigations (Chavez et al, 2000;Watanabe et al, 2001;Takahashi et al, 2002). Generally, a decrease in salivary flow and in salivary components is observed in experimental animals and diabetic patients (Anderson and Shapiro, 1980;Chavez et al, 2000).…”

Expression of BMP7 is associated with resistance to diabetic stress: Comparison among mouse salivary glands

“…Saliva was collected as described previous ly (Watanabe et al, 2001). Briefly, the mice, anesthetized with pentobarbital sodium (50 mg/kg i.p), were secured in a supine position, and a tracheal tube was inserted to support respiration.…”

“…The transcripts for BMP7 are mediated via its specific receptor, ALK2, and non-specific receptor, ALK3 (Maric et al, 2003). 4 An earlier study demonstrated that the submandibular gland was more strongly resistant to diabetic stress than the other salivary gland s (Watanabe et al, 2001). These results suggested differences in sensibility, producibility, or expression of BMP7 in salivary gland.…”