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Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium.
J Physiol. 2009 Jul 15; 587(Pt 14):3523-38.JP

Abstract

The guinea pig bladder is innervated by at least five distinct major classes of extrinsic sensory neurons. In this study, we have examined the mechanisms of mechanotransduction and chemosensitivity of two classes of bladder afferents that have their endings in the vicinity of the urothelium: stretch-sensitive muscle-mucosal mechanoreceptors and stretch-insensitive, mucosal high-responding afferents. The non-selective P2 purinoreceptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid did not affect stretch- or stroking-induced firing of these afferents but significantly reduced the excitatory action of alpha,beta-methylene ATP. Blocking synaptic transmission in Ca(2+)-free solution did not affect stretch-evoked firing but slightly reduced stretch-induced tension responses. Stroking-induced firing of both classes of afferents was also not affected in Ca(2+)-free solution. Of blockers of mechano-gated channels, benzamil (100 microM), but not amiloride (100 microM), Gd(3+) (100 microM) or SKF 96365 (50 microM), inhibited stretch- and stroking-induced firing. Serotonin (100 microM) applied directly onto receptive fields predominantly activated muscle-mucosal afferents. Muscarine (100 microM) and substance P (100 microM) in 24% and 36% cases activated only mucosal high-responding units. Bradykinin (10 microM), but not prostaglandin E2 (10 microM), excites predominantly mucosal units. High (80 mM) K(+) solution activated both afferent classes, but responses of mucosal units were 4 times greater. In contrast to muscle-mucosal units, most mucosal high-responding units were activated by hot Krebs solution (45-46 degrees C), low pH (pH 4) and capsaicin (3 microm). TRPV1 antagonist, capsazepine (10 microM) was without effect on mechanotransduction by mucosal high-responding afferents. The results show that mechanotransduction of these two types of afferents are not dependant upon Ca(2+)-dependent exocytotic release of mediators, or ATP, and it is likely that benzamil-sensitive stretch-activated ion channels on their endings are involved in direct mechanotransduction. The chemosensitivity to agonists and noxious stimuli differs significantly between these two major classes of bladder afferents that reflects their different physiological and pathophysiological roles in the bladder.

Authors+Show Affiliations

Department of Human Physiology, Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia. vladimir.zagorodnyuk@flinders.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19470774

Citation

Zagorodnyuk, Vladimir P., et al. "Mechanotransduction and Chemosensitivity of Two Major Classes of Bladder Afferents With Endings in the Vicinity to the Urothelium." The Journal of Physiology, vol. 587, no. Pt 14, 2009, pp. 3523-38.
Zagorodnyuk VP, Brookes SJ, Spencer NJ, et al. Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium. J Physiol. 2009;587(Pt 14):3523-38.
Zagorodnyuk, V. P., Brookes, S. J., Spencer, N. J., & Gregory, S. (2009). Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium. The Journal of Physiology, 587(Pt 14), 3523-38. https://doi.org/10.1113/jphysiol.2009.172577
Zagorodnyuk VP, et al. Mechanotransduction and Chemosensitivity of Two Major Classes of Bladder Afferents With Endings in the Vicinity to the Urothelium. J Physiol. 2009 Jul 15;587(Pt 14):3523-38. PubMed PMID: 19470774.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanotransduction and chemosensitivity of two major classes of bladder afferents with endings in the vicinity to the urothelium. AU - Zagorodnyuk,Vladimir P, AU - Brookes,Simon J H, AU - Spencer,Nick J, AU - Gregory,Sarah, Y1 - 2009/05/26/ PY - 2009/5/28/entrez PY - 2009/5/28/pubmed PY - 2009/10/16/medline SP - 3523 EP - 38 JF - The Journal of physiology JO - J Physiol VL - 587 IS - Pt 14 N2 - The guinea pig bladder is innervated by at least five distinct major classes of extrinsic sensory neurons. In this study, we have examined the mechanisms of mechanotransduction and chemosensitivity of two classes of bladder afferents that have their endings in the vicinity of the urothelium: stretch-sensitive muscle-mucosal mechanoreceptors and stretch-insensitive, mucosal high-responding afferents. The non-selective P2 purinoreceptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid did not affect stretch- or stroking-induced firing of these afferents but significantly reduced the excitatory action of alpha,beta-methylene ATP. Blocking synaptic transmission in Ca(2+)-free solution did not affect stretch-evoked firing but slightly reduced stretch-induced tension responses. Stroking-induced firing of both classes of afferents was also not affected in Ca(2+)-free solution. Of blockers of mechano-gated channels, benzamil (100 microM), but not amiloride (100 microM), Gd(3+) (100 microM) or SKF 96365 (50 microM), inhibited stretch- and stroking-induced firing. Serotonin (100 microM) applied directly onto receptive fields predominantly activated muscle-mucosal afferents. Muscarine (100 microM) and substance P (100 microM) in 24% and 36% cases activated only mucosal high-responding units. Bradykinin (10 microM), but not prostaglandin E2 (10 microM), excites predominantly mucosal units. High (80 mM) K(+) solution activated both afferent classes, but responses of mucosal units were 4 times greater. In contrast to muscle-mucosal units, most mucosal high-responding units were activated by hot Krebs solution (45-46 degrees C), low pH (pH 4) and capsaicin (3 microm). TRPV1 antagonist, capsazepine (10 microM) was without effect on mechanotransduction by mucosal high-responding afferents. The results show that mechanotransduction of these two types of afferents are not dependant upon Ca(2+)-dependent exocytotic release of mediators, or ATP, and it is likely that benzamil-sensitive stretch-activated ion channels on their endings are involved in direct mechanotransduction. The chemosensitivity to agonists and noxious stimuli differs significantly between these two major classes of bladder afferents that reflects their different physiological and pathophysiological roles in the bladder. SN - 1469-7793 UR - https://www.unboundmedicine.com/medline/citation/19470774/Mechanotransduction_and_chemosensitivity_of_two_major_classes_of_bladder_afferents_with_endings_in_the_vicinity_to_the_urothelium_ L2 - https://doi.org/10.1113/jphysiol.2009.172577 DB - PRIME DP - Unbound Medicine ER -