Alterations in urinary bladder M2-muscarinic receptor protein and mRNA in 2-week streptozotocin-induced diabetic rats

Tong, Yat-Ching; Chin, Wan Tai; Cheng, Juei Tang

doi:10.1016/s0304-3940(99)00871-x

Cited by 54 publications

(36 citation statements)

References 18 publications

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“…In the animal model of diabetes, the M2 receptor is significantly up-regulated in the bladder, lung, and trachea tissues in diabetes (Belmonte et al, 1997;Tong et al, 1999;Coulson et al, 2002). Since the M2 receptor is the major muscarinic subtype in the spinal cord, we also determined the change in the M2 subtype in the spinal cord in diabetics.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of Spinal Muscarinic Receptors and Increased Antinociceptive Effect of Intrathecal Muscarine in Diabetic Rats

Chen

Pan²

2003

J Pharmacol Exp Ther

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Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors produce effective pain relief. Intrathecal injection of a small dose of neostigmine produces a profound antiallodynic effect in rats with diabetic neuropathy. However, the mechanisms of increased antinociceptive effect of cholinergic agents on diabetic neuropathic pain are not clear. In the present study, we tested the hypothesis that spinal muscarinic receptors are up-regulated in diabetes. The withdrawal threshold of the hindpaw in response to noxious heat and pressure stimuli was determined in streptozotocin-induced diabetic and age-matched normal rats. 3 H]AF-DX 384 membrane binding was performed to determine the number and affinity of spinal cord M2 muscarinic receptors in normal and diabetic rats. We found that the antinociceptive effect of intrathecal 2 to 12 g muscarine in diabetic animals was potentiated significantly compared with that in normal animals. The maximal muscarine-stimulated [35 S]GTP␥S binding was 112.5 Ϯ 8.3% in normal rats and 168.8 Ϯ 12.1% (P Ͻ 0.05) in diabetic rats. Although the K D value (2.9 nM) was similar in both groups, the B max of [ 3 H]AF-DX 384 membrane binding was significantly higher in diabetic than in normal rats (255.2 Ϯ 5.9 versus 165.9 Ϯ 3.5 fmol/mg protein, P Ͻ 0.05). Collectively, these data strongly suggest that the muscarinic receptor is up-regulated in the dorsal spinal cord in diabetic rats. This finding probably accounts for the increased efficacy of the antinociceptive effect of intrathecal muscarinic agonists in diabetic neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Up-Regulation of Spinal Muscarinic Receptors and Increased Antinociceptive Effect of Intrathecal Muscarine in Diabetic Rats

Chen

Pan²

2003

J Pharmacol Exp Ther

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“…In bladders from diabetic animals, an increased density of muscarinic receptors accompanied by an enhanced muscarinic receptor-mediated phosphoinositide hydrolysis was found (Latifpour et al, 1989;Mimata et al, 1995). An up-regulation of M 2 receptor mRNA has been demonstrated in rats with streptozotocin-induced diabetes (Tong et al, 1999), and also a supersensitivity of postjunctional muscarinic receptors may develop . However, it is unclear what these receptor changes mean for the functional bladder disorders seen in diabetic patients.…”

Section: Peripheral Targetsmentioning

confidence: 99%

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Andersson

Wein²

2004

Pharmacol Rev

454

364

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“…Interestingly, Tong et al (1999) also demonstrated an upregulation in M 2 receptor mRNA. 13 Nevertheless, its significance in diabetes bladder dysfunction remains ill understood. Another potential mechanism for altered properties of the diabetic urinary bladder tissue could be due to impaired nitric oxide control.…”

Section: Fig6: Represents Images Of Haematoxylin and Eosin Stained Smentioning

confidence: 91%

“…8,24,25 Indeed, the former was suggested by Tong et al (1999) who reported significant increases in the quantity of M 3 mAChR protein in the STZ-induced diabetic rat urinary bladder in comparison to the control urinary bladder. Interestingly, Tong et al (1999) also demonstrated an upregulation in M 2 receptor mRNA. 13 Nevertheless, its significance in diabetes bladder dysfunction remains ill understood.…”

Section: Fig6: Represents Images Of Haematoxylin and Eosin Stained Smentioning

confidence: 91%

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Sangar¹,

Shakil²,

Singh³

2016

IJPSR

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ABSTRACT:Patients with DM are often afflicted by debilitating urologic complications. The main aim of this study is to investigate the effect of streptozotocin (STZ)-induced type I diabetes on contractile responses to numerous stimuli, intracellular cation concentrations and morphology in the rat. Adult rats (n=12) were humanely killed and detrusor muscles of urinary bladder located and excised rapidly and placed in organ baths. Then urinary bladder detrusor muscles were blotted, weighed and dissolved in concentrated nitric acid for the measurements of cation contents. The diabetic rats had significantly (P<0.05) elevated blood glucose compared to control rats. The contractile responses induced by EFS were significantly (P<0.05) increased in the diabetic urinary bladder tissue in comparison to the control urinary bladder tissue. The increase in the contractile force was calcium-dependent in both control and diabetic urinary bladder tissues. The results also showed no significant differences in the levels of sodium, potassium, calcium, between the diabetic and control urinary bladder (p>0.05). However, there was a significant (P<0.05) decrease in magnesium in the diabetic urinary bladder tissue in comparison to the control urinary bladder tissue. The increased responsiveness of the diabetic urinary bladder tissue compared to the control tissue may be due to either alterations in the intracellular cation concentrations, hypertrophy of the diabetic urinary bladder or calcium sensitivity to the myofilaments. The results also raise the possibility that that these factors, in conjunction with other causes may work in tandem to exacerbate diabetic bladder dysfunction.

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Alterations in urinary bladder M2-muscarinic receptor protein and mRNA in 2-week streptozotocin-induced diabetic rats

Cited by 54 publications

References 18 publications

Up-Regulation of Spinal Muscarinic Receptors and Increased Antinociceptive Effect of Intrathecal Muscarine in Diabetic Rats

Up-Regulation of Spinal Muscarinic Receptors and Increased Antinociceptive Effect of Intrathecal Muscarine in Diabetic Rats

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

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