Lowered susceptibility of muscarinic receptor involved in salivary secretion of streptozotocin-induced diabetic rats.
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 [3H]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 [3H]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.
Watanabe
M
M
Department of Pharmacology, Tokyo Dental College, Chiba, Japan.
Yamagishi-Wang
H
H
Kawaguchi
M
M
D000818:Animals; D001667:Binding, Competitive; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D018721:Muscarinic Agonists / Q000494:pharmacology; D010306:Parotid Gland / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010862:Pilocarpine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012463:Saliva / Q000187:drug effects / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D013363:Submandibular Gland / Q000737:chemistry; D014868:Water Deprivation
D001786:Blood Glucose; D007328:Insulin; D008565:Membrane Proteins; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D010862:Pilocarpine