In Vitro Effects of Bladder Mucosa and an Enkephalinase Inhibitor on Tachykinin Induced Contractility of the Dog Bladder

Saban, Ricardo; Keith, Ingegerd M.; Nielsen, K.; Christensen, Mads M.; Rhodes, Patsy R.; Bruskewitz, Reginald C.

doi:10.1016/s0022-5347(17)37372-x

Cited by 27 publications

(21 citation statements)

References 20 publications

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“…In rat bladders, surgical removal of the bladder mu cosa significantly increases the contractile re sponse to substance P, but not to KC1 or his tamine [22], The potentiating effect of muco sa removal on substance P is thought to be due to removal of a diffusion barrier or to loss of metabolizing enzymes. Similarly in dog bladder, removal of the bladder mucosa in creases the maximal contractile responses of bladder strips to the tachykinins, neurokinin A and B, and to substance P. but not to carbachol [23]. However, in control rats, treatment of bladder strips with collagenase to remove the mucosa is without effect on the contractile response to bradykinin [24], Therefore re moval of the mucosa seems to specifically enhance the response to some tachykinins, but not to all.…”

Section: Discussionmentioning

confidence: 94%

The Role of the Mucosa in the in vitro Changes in Guinea Pig Bladder Function Which Occur after Sensitization with Ovalbumin

Krasnopolsky

Levin²,

Longhurst³

1995

Pharmacology

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Bladder strips from sensitized guinea pigs respond to ovalbumin challenge with a contraction accompanied by release of histamine, prostaglandin, and leukotriene. Histamine and prostaglandin release occurs preferentially from the bladder mucosa, while leukotrienes are released by the smooth muscle. This study investigated the effects of removal of the bladder mucosa on contractile responses of strips from control and sensitized guinea pigs to electrical stimulation and to contractile agonists. Removal of the mucosa potentiated the contractile response to electrical stimulation at low voltages and pulse durations. The presence of ovalbumin had no effects on the response to electrical stimulation. Removal of the mucosa had no effect on the contractile responses of bladder strips to bethanechol, histamine, KC1, or ovalbumin, although after correction for the decreased strip mass after mucosa removal there was a tendency for the responses to increase. We conclude that the responsiveness of bladder strips from sensitized guinea pigs to ovalbumin challenge results primarily from effects which occur within the smooth muscle.

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Section: Discussionmentioning

confidence: 94%

The Role of the Mucosa in the in vitro Changes in Guinea Pig Bladder Function Which Occur after Sensitization with Ovalbumin

Krasnopolsky

Levin²,

Longhurst³

1995

Pharmacology

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“…Studies to date have provided evidence for [11] and against [12] a role of peptidases in regulating contractile responses to the tachykinins in the rat urinary bladder. In other species (human, dog and guinea-pig) it was reported that the responsiveness of urinary bladder smooth muscle strips to tachykinins was enhanced in the presence of peptidase inhibitors [8][9][10]. It would appear therefore that there are species differences in peptidase activity in the urinary bladder.…”

Section: Discussionmentioning

confidence: 99%

“…Once released from afferent nerves, the activity of tachykinins at their receptors can be modulated by peptidases. While there is considerable evidence in several species that peptidases modulate the contractile responses to tachykinins in the urinary bladder [8][9][10] there is less clarity about peptidases as regulators of the biological activity of tachykinins in the rat urinary bladder [11,12].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of neurokinin A‐ and substance P‐induced contractions in rat detrusor smooth muscle in vitro

2004

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(1 m mol/L), peptidase inhibitors (captopril, thiorphan and bestatin; 1 m mol/L each) or piroxicam (10 m mol/L). The rank order of potency of agonists was neurokinin A > substance P > carbachol. Contractile responses to neurokinin A and substance P, like the contractile responses to carbachol, were abolished in a nominally Ca 2+-free medium and significantly reduced by nifedipine (1 m mol/L). SKF-96365 (60 m mol/L), an inhibitor of receptor-mediated Ca 2+ entry, abolished the nifedipine-resistant response to substance P and carbachol, and significantly attenuated the response to neurokinin A. Depleting intracellular Ca 2+ stores with thapsigargin (1 m mol/L) significantly attenuated neurokinin A-induced contractions but had no effect on substance P-or carbachol-induced contractions. The Rho-kinase inhibitor, Y-27632 (10 m mol/L), significantly reduced both phasic and tonic components of the contractile responses to neurokinin A, substance P and carbachol. CONCLUSIONThe contractile responses induced by tachykinins in rat urinary bladder smooth muscle strips involve a direct action on smooth muscle and are not modulated by peptidases or prostanoids. Neurokinin A and substance P, like carbachol-induced contractions, depend on extracellular Ca 2+ influx largely through voltage-operated and partly through receptor-operated Ca 2+ channels. Intracellular Ca 2+ release contributes to the contractile response to neurokinin A but appears to have no involvement in substance P-and carbacholinduced contractions. Rho-kinase activation contributes to contractions induced by substance P, neurokinin A and carbachol.

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“…In some species, neurons are additionally present within the wall of the urinary bladder itself. Such intramural ganglia have been demonstrated to be present in the bladder of guineapigs (James & Burnstock, 1990;Lincoln & Burnstock, 1993), cats (Hamberger & Norberg, 1965;Feher et al, 1979), horses (Prieto et al, 1989), dogs (Saban et al, 1992), and humans (Dixon et al, 1983;Gu et al, 1984a;Smet et al, 1994b), but are either absent or very sparse in mice (Grozdanovic et al, 1992), rats (Gabella & Uvelius, 1990;Lincoln & Burnstock, 1993) and pigs (Crowe & Burnstock, 1989). These intrinsic neurons are thought to represent an extension of the pelvic plexus (Dixon et al, 1983), and to function primarily as simple parasympathetic relay stations.…”

Section: Introductionmentioning

confidence: 99%

Neuropeptides and neurotransmitter-synthesizing enzymes in intrinsic neurons of the human urinary bladder

et al. 1996

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The expression of neuropeptides, and the enzymes nitric oxide synthase and tyrosine hydroxylase were examined in intramural ganglia of human urinary bladder using single label immunocytochemistry. Scattered ganglia composed of between 1-36 neurons (median 4) were observed in all layers of the lateral wall of the bladder. These contained immunoreactivity to vasoactive intestinal peptide, nitric oxide synthase, neuropeptide Y, and galanin. Neurons within the bladder were heterogeneous with regard to their content of these antigens, with the proportion of immunopositive cells ranging from 58-84%. Occasional neurons with immunoreactivity to the catecholamine-synthesizing enzyme, tyrosine hydroxylase, were also observed. No cell somata, however, were immunoreactive for enkephalin, substance P, calcitonin gene-related peptide or somatostatin. Varicose terminals entering the ganglia were seen to form pericellular baskets surrounding some of the principal ganglion cells. The most prominent pericellular varicosities were those containing calcitonin gene-related peptide- or vasoactive intestinal peptide-immunoreactivity, followed by those with immunoreactivity for enkephalin, neuropeptide Y, or galanin. Less common were pericellular varicosities with substance P-immunoreactivity, which may represent collateral processes of unmyelinated primary sensory fibres, and presumptive noradrenergic processes containing tyrosine hydroxylase. Some calcitonin gene-related peptide-immunoreactive varicosities constituted a distinct type, terminating as large pericellular boutons 2-4 microns in diameter. Fibres containing nitric oxide synthase- or somatostatin-immunoreactivity were not associated with the intramural neurons. The results demonstrate that intrinsic neurons within the human urinary bladder express a number of neuroactive chemicals, and could in principle form circuits with the potential to support integrative activity.

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In Vitro Effects of Bladder Mucosa and an Enkephalinase Inhibitor on Tachykinin Induced Contractility of the Dog Bladder

Cited by 27 publications

References 20 publications

The Role of the Mucosa in the in vitro Changes in Guinea Pig Bladder Function Which Occur after Sensitization with Ovalbumin

The Role of the Mucosa in the in vitro Changes in Guinea Pig Bladder Function Which Occur after Sensitization with Ovalbumin

Mechanisms of neurokinin A‐ and substance P‐induced contractions in rat detrusor smooth muscle in vitro

Neuropeptides and neurotransmitter-synthesizing enzymes in intrinsic neurons of the human urinary bladder

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