Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder

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Abstract

Acetylcholine, and to a lesser extent ATP, mediates neurogenic contractions of bladder smooth muscle. Recently, the urothelium and lamina propria have also been shown to have contractile properties, but the neurotransmitters involved in mediating responses to nerve stimulation have not been investigated. Isolated strips of porcine urothelium with lamina propria were electrically field stimulated and contractions recorded. Drugs interfering with neurotransmission were then employed to identify which neurotransmitters mediated responses. Strips of urothelium/lamina propria developed spontaneous contractions with a frequency of 3.5 ± 0.1 cycles min -1 and amplitude of 0.84 ± 0.06 g. Electrical field stimulation at 5, 10, and 20 Hz resulted in frequency-related contractions (1.13 ± 0.36 g, 1.59 ± 0.46 g and 2.20 ± 0.53 g, respectively, n = 13), and these were reduced in the presence of tetrodotoxin (1 μm) by 77 ± 20% at 5 Hz, 79 ± 7% at 10 Hz and 74 ± 12% at 20 Hz (all P < 0.01), indicating they were predominantly neurogenic in nature. Neither the muscarinic antagonist atropine (10 μm), the adrenergic neurone blocker guanethidine (10 μm) nor desensitization of the purinergic receptors with α,β-methylene ATP (10 μm) affected the contractile amplitude. Similarly, responses were not affected by the nitric oxide synthase inhibitor l-NNA (100 μm) or drugs that interfere with peptide neurotransmission (capsaicin, NK2 antagonist GR159897, protease inhibitors). In conclusion, electrical depolarization of the nerves present in the porcine urothelium/lamina propria results in frequency-dependent contractions, which are predominantly neurogenic in nature. These contractions are resistant to drugs that inhibit the adrenergic, cholinergic and purinergic systems. The neurotransmitter involved in the responses of this tissue is therefore unknown but does not appear to be a peptide.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalAutonomic and Autacoid Pharmacology
Volume32
Issue number3 PART 4
DOIs
Publication statusPublished - Oct 2012

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Urothelium
Mucous Membrane
Urinary Bladder
Swine
Neurotransmitter Agents
Synaptic Transmission
Adenosine Triphosphate
Purinergic Receptors
Guanethidine
Adrenergic Neurons
Neurogenic Urinary Bladder
Peptides
Muscarinic Antagonists
Adrenergic Antagonists
Capsaicin
Tetrodotoxin
Protease Inhibitors
Atropine
Nitric Oxide Synthase
Pharmaceutical Preparations

Cite this

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title = "Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder",
abstract = "Acetylcholine, and to a lesser extent ATP, mediates neurogenic contractions of bladder smooth muscle. Recently, the urothelium and lamina propria have also been shown to have contractile properties, but the neurotransmitters involved in mediating responses to nerve stimulation have not been investigated. Isolated strips of porcine urothelium with lamina propria were electrically field stimulated and contractions recorded. Drugs interfering with neurotransmission were then employed to identify which neurotransmitters mediated responses. Strips of urothelium/lamina propria developed spontaneous contractions with a frequency of 3.5 ± 0.1 cycles min -1 and amplitude of 0.84 ± 0.06 g. Electrical field stimulation at 5, 10, and 20 Hz resulted in frequency-related contractions (1.13 ± 0.36 g, 1.59 ± 0.46 g and 2.20 ± 0.53 g, respectively, n = 13), and these were reduced in the presence of tetrodotoxin (1 μm) by 77 ± 20{\%} at 5 Hz, 79 ± 7{\%} at 10 Hz and 74 ± 12{\%} at 20 Hz (all P < 0.01), indicating they were predominantly neurogenic in nature. Neither the muscarinic antagonist atropine (10 μm), the adrenergic neurone blocker guanethidine (10 μm) nor desensitization of the purinergic receptors with α,β-methylene ATP (10 μm) affected the contractile amplitude. Similarly, responses were not affected by the nitric oxide synthase inhibitor l-NNA (100 μm) or drugs that interfere with peptide neurotransmission (capsaicin, NK2 antagonist GR159897, protease inhibitors). In conclusion, electrical depolarization of the nerves present in the porcine urothelium/lamina propria results in frequency-dependent contractions, which are predominantly neurogenic in nature. These contractions are resistant to drugs that inhibit the adrenergic, cholinergic and purinergic systems. The neurotransmitter involved in the responses of this tissue is therefore unknown but does not appear to be a peptide.",
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Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder. / Moro, C.; Chess-Williams, R.

In: Autonomic and Autacoid Pharmacology, Vol. 32, No. 3 PART 4, 10.2012, p. 53-59.

Research output: Contribution to journalArticleResearchpeer-review

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