Prostaglandin-release impairment in the bladder epithelium of streptozotocin-induced diabetic rats

Pinna, Christian; Zanardo, Rossella; Puglisi, L.

doi:10.1016/s0014-2999(99)00833-x

Cited by 52 publications

(39 citation statements)

References 15 publications

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“…The structural conformation of the polyphosphate chain of the ATP molecule is critical for stimulation of PG biosynthesis [92]. ATP can also lead to production of prostanoids in uroepithelial cells of the bladder, an affect which is enhanced in pathological conditions [565]. PGE 2 production was significantly increased in the guineap i g b l a d d e r l a m i n a p r o p r i a b y 2 ′ ( 3 ′ ) -O -( 4 -benzoylbenzoyl)adenosine 5′-triphosphate acting via both P2X and P2Y receptors [523].…”

Section: Involvement Of Prostaglandins In Purinergic Signallingmentioning

confidence: 99%

“…No significant differences were found in the sensitivity of bladder strips from control and STZ diabetic rats to antagonism by nifedipine [443]. ATP significantly increases the endogenous release of PGF 2 and PGF 2α from the urothelium of 4-week-old STZ diabetic rat bladder and it was proposed that P2X receptors are present on urothelial cells as well as smooth muscle [565]. Increased synthesis of prostanoids during epithelial irritation may produce hyperactivity or spasm of the detrusor muscle [309].…”

Section: Diabetesmentioning

confidence: 99%

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Purinergic signalling in the urinary tract in health and disease

Burnstock

2013

Purinergic Signalling

139

142

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Purinergic signalling is involved in a number of physiological and pathophysiological activities in the lower urinary tract. In the bladder of laboratory animals there is parasympathetic excitatory cotransmission with the purinergic and cholinergic components being approximately equal, acting via P2X1 and muscarinic receptors, respectively. Purinergic mechanosensory transduction occurs where ATP, released from urothelial cells during distension of bladder and ureter, acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate the voiding reflex, via low threshold fibres, and nociception, via high threshold fibres. In human bladder t h e p u r i n e rg i c c o m p o n e n t o f p a r a s y m p a t h e t i c cotransmission is less than 3 %, but in pathological conditions, such as interstitial cystitis, obstructed and neuropathic bladder, the purinergic component is increased to 40 %. Other pathological conditions of the bladder have been shown to involve purinoceptor-mediated activities, including multiple sclerosis, ischaemia, diabetes, cancer and bacterial infections. In the ureter, P2X7 receptors have been implicated in inflammation and fibrosis. Purinergic therapeutic strategies are being explored that hopefully will be developed and bring benefit and relief to many patients with urinary tract disorders.

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Section: Involvement Of Prostaglandins In Purinergic Signallingmentioning

confidence: 99%

Section: Diabetesmentioning

confidence: 99%

Purinergic signalling in the urinary tract in health and disease

Burnstock

2013

Purinergic Signalling

139

142

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“…Bladder distension is a natural mechanical stimulus to evoke sensations such as fullness, urgency, and pain while the literature suggests a complex regulatory role of prostaglandins (PGs) in multiple aspects of urinary bladder physiology/pathophysiology. PGE 2 , one of the principal PGs, is synthesized in urothelium and detrusor smooth muscle (19,24,25,27) as well as in neurons and glial cells (18,23) and is released in response to various physiological (e.g., bladder distension) and pathological (e.g., mediators of inflammation) stimulation. PGE 2 interacts with four EP receptor subtypes (EP 1 , EP 2 , EP 3 , and EP 4 ) (23).…”

mentioning

confidence: 99%

An excitatory role for peripheral EP₃ receptors in bladder afferent function

Su¹,

Lashinger²,

Leon³

et al. 2008

American Journal of Physiology-Renal Physiology

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The excitatory roles of EP3 receptors at the peripheral afferent nerve innervating the rat urinary bladder have been evaluated by using the selective EP3 antagonist (2E)-3-{1-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-1H-indol-7-yl}-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041). The bladder rhythmic contraction model and a bladder pain model measuring the visceromotor reflex (VMR) to urinary bladder distension (UBD) have been used to evaluate DG-041 in female rats. In addition, male rats [spontaneously hypertensive rat (SHR), WistarKyoto (WKY), and Sprague-Dawley (SD)] were anesthetized with pentobarbital sodium, and primary afferent fibers in the L 6 dorsal root were isolated for recording the inhibitory response to UBD following intravenous injection of DG-041. Intravenous injection of DG-041 (10 mg/kg), a peripherally restricted EP 3 receptor antagonist, significantly reduced the frequency of bladder rhythmic contraction and inhibited the VMR response to bladder distension. The magnitude of reduction of the VMR response was not different in the different strains of rats (SD, SHR, and WKY). Furthermore, quantitative characterization of the mechanosensitive properties of bladder afferent nerves in SHR, WKY, and SD rats did not show the SHR to be supersensitive to bladder distension. DG-041 selectively attenuated responses of mechanosensitive afferent nerves to UBD, with strong suppression on the slow-conducting, high-threshold afferent fibers, with equivalent activity in the three strains. We conclude that sensitization of afferent nerve activity was not one of the mechanisms of bladder hypersensitivity in SHR. EP 3 receptors are involved in the regulation of bladder micturition and bladder nociception at the peripheral level.EP3; viscermotor reflex; bladder rhythmic contraction; bladder distension; afferent nerve SENSATION ASSOCIATED WITH the urinary bladder is conveyed primarily by pelvic and hypogastric nerves, by which the signal is relayed to the central nervous system (CNS). Most afferent fibers innervating the musculature of the bladder body pass through the pelvic nerve, whereas the majority of afferent endings in the bladder submucosa are derived from the hypogastric nerve (41), suggesting that the afferent fibers in the pelvic and hypogastric nerves have different roles, signaling mechanical stimulation (e.g., bladder distension) and chemical stimulation (e.g., inflammation), respectively (20,22,30,34). Bladder distension is a natural mechanical stimulus to evoke sensations such as fullness, urgency, and pain while the literature suggests a complex regulatory role of prostaglandins (PGs) in multiple aspects of urinary bladder physiology/pathophysiology. PGE 2 , one of the principal PGs, is synthesized in urothelium and detrusor smooth muscle (19,24,25,27) as well as in neurons and glial cells (18,23) and is released in response to various physiological (e.g., bladder distension) and pathological (e.g., mediators of inflammation) stimulation. PGE 2 interacts with four EP receptor subt...

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“…Nevertheless, the results of histology, in the context of the wider question, suggest differences in the contractile responses may be due to either increased quantity of urothelium or smooth muscle mass. The results of the study conducted by Pinna and colleagues 14 suggest that the diabetic urinary bladder in part, requires prostaglandin release from the urothelium to activate purinergic receptors. Implying the increased urothelium mass may play a role in the abnormalities seen in this, and many other studies employing the diabetic urinary bladder tissue.…”

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

confidence: 99%

“…13,9 Moreover, morphological studies are indicative of a progressive hypertrophy of the urothelium of the urinary bladder in diabetes. 14,15 However, the importance of this on the mechanisms of urologic complications remains ill understood.…”

Section: Introductionmentioning

confidence: 99%

Untitled

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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Prostaglandin-release impairment in the bladder epithelium of streptozotocin-induced diabetic rats

Cited by 52 publications

References 15 publications

Purinergic signalling in the urinary tract in health and disease

Purinergic signalling in the urinary tract in health and disease

An excitatory role for peripheral EP₃ receptors in bladder afferent function

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Prostaglandin-release impairment in the bladder epithelium of streptozotocin-induced diabetic rats

Cited by 52 publications

References 15 publications

Purinergic signalling in the urinary tract in health and disease

Purinergic signalling in the urinary tract in health and disease

An excitatory role for peripheral EP3 receptors in bladder afferent function

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An excitatory role for peripheral EP₃ receptors in bladder afferent function