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N Dass

Publications and source records attributed to N Dass.

10 recordsLinked to original sources
PubMed2002

GABA(B) receptor function in the ileum and urinary bladder of wildtype and GABA(B1) subunit null mice.

1. GABA(B1) receptor subunit knockout mice were generated and the effects of the GABA(B) receptor agonist, baclofen, were evaluated within the peripheral nervous system (PNS) of wildtype (+/+), heterozygote (+/-) and knockout (-/-) animals. For this purpose, neuronally-mediated responses were evoked in both the isolated ileum and urinary bladder, using selective electrical field stimulation (EFS). 2. In ileum resected from 4-8-week-old-mice, low frequencies of EFS (0.5 Hz) evoked irregular muscle contractions which were prevented by atropine 1 microM and reduced by baclofen (33.4 +/- 5.6%, 100 microm). The latter effect was antagonized by the GABA(B) receptor antagonist CGP54626 0.2 microm. Baclofen 100 microm did not affect contractions of similar amplitude induced by carbachol, indicating that the ability of baclofen to inhibit cholinergic function in mouse ileum may be due to an action at prejunctional GABA(B) receptors. 3. To avoid the development of grand mal seizure by GABA(B1) (-/-) mice, a behaviour observed when the mice were greater than 3 weeks old, it was necessary to study the effects of this knockout in 1-3-week-old-animals. However, at this age, EFS at 0.5 Hz did not evoke robust muscle contractions. Consequently we used EFS at 5 Hz, which did evoke cholinergically mediated contractions, found to be of similar amplitude in (+/+) and (+/-) mice, of both 1-3 weeks and 4-8 weeks of age. At this frequency of EFS, baclofen reduced the amplitude of the evoked contractions [n = 6 (+/+) and n = 5 (+/-), IC50 19.2 +/- 4.8 microm) and this effect was greatly reduced in the presence of CGP54626 0.2 microm. 4. In urinary bladder from 1-3-week-old-mice, using higher frequencies of EFS to evoke clear, nerve-mediated contractions (10 Hz), baclofen 10-300 microm concentration-dependently inhibited contractions in (+/+) mice (IC50 9.6 +/- 3.8 microm). This effect was inhibited by CGP54626 (0.2 microm, 46.2 +/- 13.6% inhibition, 300 microm baclofen n = 7) a concentration which, by itself, had no effect on the EFS-evoked contractions. 5. The effects of baclofen in both ileum and urinary bladder were absent in the GABA(B1) receptor subunit (-/-) mice; however, responses to EFS were unaffected in (-/-) when compared to the (+/+) mice. 6. Our data suggest that, as in the central nervous system (CNS), the GABA(B1) receptor subunit is an essential requirement for GABA(B) receptor function in the enteric and PNS. As such, these data do not provide a structural explanation for the existence of putative subtypes of GABA(B) receptor, suggested by studies such as those in which different rank-orders of GABA(B) agonist affinity have been reported in different tissues.

Animals↗
PubMed2001

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores.

While nicotine is known to act at neuronal nicotinic acetylcholine receptors (nAChRs) to facilitate neurotransmitter release, the mechanisms underlying this action are poorly understood. Some of its effects are known to be mediated by presynaptic receptors. In the mouse vas deferens nicotine (10-30 microM) transiently increased the force of neurogenic contraction by 135+/-25%, increased the amplitude of excitatory junction potentials by 74+/-6% and increased the frequency of spontaneous excitatory junction potentials in four out of six preparations. Confocal microscopy and the calcium indicator Oregon Green 488 BAPTA-1 dextran were used to measure calcium concentration changes in the nerve terminals. Nicotine did not affect the action potential-evoked calcium transient but instead triggered small, random fluctuations ("calcium spikes") in intra-varicosity calcium concentrations at an average frequency of 0.09+/-0.02 Hz. These were insensitive to tetrodotoxin at a concentration that blocked action-potential evoked calcium transients (300 nM). They were abolished by the nAChR blocker hexamethonium (100 microM) and by both ryanodine (100 microM) and caffeine (3 mM), agents that modify calcium release from intracellular stores. We propose a novel mechanism whereby nicotine's action at nAChRs triggers calcium-induced calcium release from a ryanodine-sensitive calcium store in nerve terminals. This primes neurotransmitter release mechanisms and enhances both spontaneous and action potential-evoked neurotransmitter release.

Adrenergic alpha-Antagonists↗
PubMed2001

Morphological and physiological characteristics of urethral circular and longitudinal smooth muscle.

The urethral wall contains circular and longitudinal smooth muscle. Both layers can develop spontaneous tone, and contract further or relax in response to excitatory or inhibitory stimuli. In the pig the cells do not generate action potentials, and the membranes possess L-type calcium channels and a variety of potassium channels which may modulate the membrane potential and tone. The importance of these layers in generating the urethral pressure is not well understood in the human, but it seems likely that the circular smooth muscle is involved in generating urethral pressure in the pig.

Animals↗
PubMed2001

Morphological aspects of the female pig bladder neck and urethra: quantitative analysis using computer assisted 3-dimensional reconstructions.

PURPOSE: To investigate whether the pig is a suitable model for studies of lower urinary tract function and dysfunction, we sought to determine the morphology of the female pig bladder neck and urethra. Computer assisted 3-dimensional (D) reconstructions from step serial histological sections were used for visualization of the spatial relationships between neighboring urethral wall components, and the quantification of these components in the bladder neck and along the urethra. MATERIALS AND METHODS: Step serial histological paraffin sections from the bladder neck and urethra of 6 female pigs, stained with Masson's trichrome, were used to generate computer assisted 3-D reconstructions using MacStereology (Ranfurly MicroSystems Ltd., Airdrie, United Kingdom) as the 3-D software package. RESULTS: The bladder neck and urethral anatomy revealed well defined smooth and striated muscle layers that varied in location, regional distribution and orientation. Circular smooth muscle was maximally developed in the mid urethra, at which point maximal urethral pressure was observed. The longitudinal smooth muscle layer appeared continuous with the detrusor, implicating a possible role in urethral shortening at the onset of voiding. A small circular and longitudinal striated muscle component was present in the distal urethra. CONCLUSIONS: Anatomical differences exist between the female pig and human bladder neck and urethra, which were successfully highlighted using computer assisted 3-D reconstructions from step serial histological paraffin sections.

Animals↗
PubMed1999

Elastic fibres in the vesicourethral junction and urethra of the guinea pig: quantification with computerised image analysis.

Elastic fibres, which are intimately associated with collagen, a major component of the urethra, have been assumed to contribute to the resting urethral closure pressure. The Miller stain for elastin was used to demonstrate elastic fibres in cryostat sections of guinea pig bladder base, vesicourethral junction (VUJ) and urethra. Computerised image analysis was employed to objectively quantify these fibres. Both male and female guinea pigs showed significantly greater amounts of circularly disposed elastic fibres in the VUJ than in the other 2 regions examined. This particular disposition of fibres may be responsible for imparting resiliency and plasticity to the VUJ, allowing it to distend and recoil repeatedly in response to urine outflow. Furthermore, the elastic fibres may be partly responsible for the passive occlusive force in this region. Elastic fibres in the distal urethra were not quantified because of their relative paucity. Sagittal sections of the urethra revealed a mass of longitudinally arranged elastic fibres localised almost exclusively within the mucosa, submucosa and longitudinal smooth muscle layer. Functionally, this arrangement may exist to facilitate urethral length changes that occur in micturition.

Animals↗
PubMed1999

alpha1-adrenoceptors in urethral function.

The external urethral sphincteric mechanism generates forces which seal the urethra and can be measured as urethral pressure. Resting pressure can be augmented transiently through a reflex pathway during increases in intra-abdominal pressure. The exact role of the various components of the urethral wall that generate this pressure is so far unknown. Urethral contributions to continence come from the mucosal hermetic seal, the submucosa and its vascular filling and the smooth and striated muscle. In humans alpha1-adrenoceptor antagonists can reduce urethral pressure, whereas agonists have little effect. A significant part of urethral resting tone is thought to be mediated through the smooth muscles. In vitro, longitudinal and circular smooth muscle components possess spontaneous tone and are innervated by excitatory and inhibitory nerves. Both types possess alpha1-adrenoceptors and contract on stimulation of intrinsic sympathetic nerves or application of alpha1-adrenoceptor agonists. In human urethra, longitudinal smooth muscle predominates but its functional role is unclear. alpha1 stimulation may also affect the vasculature of the submucosa, the striated muscle of the urethra or transmitter release from neurones in the control pathways. Insufficient knowledge of alpha1-adrenoceptor distribution and function within the urethra and the surrounding tissues currently prevents accurate prediction of the therapeutic potential of alpha1-adrenoceptor ligands.

Animals↗
PubMed1998

Purinoceptor subtypes mediating contraction and relaxation of marmoset urinary bladder smooth muscle.

1. The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), alpha,beta-methylene-ATP (alpha,beta-MeATP) and 2-methylthio-ATP (2-MeSATP) on longitudinally orientated smooth muscle strips from marmoset urinary bladder were investigated by use of standard organ bath techniques. 2. After being mounted in superfusion organ baths, 66.7% (n=249) of marmoset detrusor smooth muscle strips developed spontaneous tone, 48.2% of all strips examined developed tone equivalent to greater than 0.1 g mg(-1) of tissue and were subsequently utilized in the present investigation. 3. On exposure to ATP, muscle strips exhibited a biphasic response, a rapid and transient contraction followed by a more prolonged relaxation. Both responses were found to be concentration-dependent. ADP and 2-MeSATP elicited a similar response (contraction followed by relaxation), whereas application of alpha,beta-MeATP only produced a contraction. The potency order for each effect was alpha,beta-MeATP> >2-MeSATP> ATP>ADP (contractile response) and ATP=2-MeSATP> or = ADP> > alpha,beta-MeATP (relaxational response). 4. Desensitization with alpha,beta-MeATP (10 microM) abolished the contractile phase of the response to ATP, but had no effect on the level of relaxation evoked by this agonist. On the other hand, the G-protein inactivator, GDPbetaS (100 microM) abolished only the relaxation response to ATP. Suramin (general P2 antagonist, 100 microM) shifted both the contractile and relaxation ATP concentration-response curves to the right, whereas cibacron blue (P2Y antagonist, 10 microM) only antagonized the relaxation response to ATP. In contrast, the adenosine receptor antagonist, 8-phenyltheophylline (10 microM), had no effect on the relaxation response curve to ATP. 5. Incubation with tetrodotoxin (TTX, 3 microM) or depolarization of the muscle strip with 40 mM K+ Krebs failed to abolish the relaxation to ATP. In addition, neither Nomega-nitro-L-arginine (L-NOARG, 10 microM) nor methylene blue (10 microM) had any effect on the relaxation response curve. However, tos-phe-chloromethylketone (TPCK, 3 microM), an inhibitor of cyclicAMP-dependent protein kinase A (PKA), significantly (P<0.01) shifted the curve for the ATP-induced relaxation to the right. 6. It is proposed that marmoset detrusor smooth muscle contains two receptors for ATP, a classical P2X-type receptor mediating smooth muscle contraction, and a P2Y (G-protein linked) receptor mediating smooth muscle relaxation. The results also indicate that the ATP-evoked relaxation may occur through the activation of cyclicAMP-dependent PKA.

Adenosine Diphosphate↗
PubMed1996

Intrinsic urethral closure mechanisms in the female pig.

This study investigates the role of the various components of the female pig urethral wall in the generation of the urethral closure pressure. Prior to voiding urethral pressure fails and this is accompanied by a rise in lamina propria blood flow. Pharmacological manipulation shows that striated muscle is not involved in the generation of the urethral closure pressure. Drugs active upon smooth muscle change urethral pressure significantly by a mechanism independent of their cardiovascular system effects. Histological studies show that it is possible to correlate the disposition of circular smooth muscle with the urethral pressure profile. In vitro smooth muscle from the high pressure zone is pharmacologically different to that from the proximal urethra in a manner which may reflect their physiological roles.

Animals↗