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ATP and P2X Purinoceptors in Urinary Tract Disorders

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Book cover Urinary Tract

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 2011))

Abstract

The pharmacological concept of specifically targeting purinoceptors (receptors for ATP and related nucleotides) has emerged over the last two decades in the quest for novel, differentiated therapeutics. Investigations from many laboratories have established a prominent role for ATP in the functional regulation of most tissue and organ systems, including the urinary tract, under normal and pathophysiological conditions. In the particular case of the urinary tract, ATP signaling via P2X1 receptors participates in the efferent control of detrusor smooth muscle excitability, and this function may be heightened in disease and aging. Perhaps of greater interest, ATP also appears to be involved in bladder sensation, operating via activation of P2X3-containing receptors on sensory afferent neurones, both on peripheral terminals within the urinary tract tissues (e.g., ureters, bladder) and on central synapses in the dorsal horn of the spinal cord. Such findings are based on results from classical pharmacological and localization studies in nonhuman and human tissues, gene knockout mice, and studies using recently identified pharmacological antagonists – some of which have progressed as candidate drug molecules. Based on recent advances in this field, it is apparent that the development of selective antagonists for these receptors will occur that could lead to therapies offering better relief of storage, voiding, and sensory symptoms for patients, while minimizing the systemic side effects that curb the clinical effectiveness of current urologic medicines.

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Abbreviations

ADP:

Adenosine 5′-diphosphate

AMP:

Amplitude of contractions

ATP:

Adenosine 5′-triphosphate

BPH:

Benign prostatic hyperplasia

BPS/IC:

Bladder pain syndrome/interstitial cystitis

BzATP:

2′(3′)-O-(4-benzoylbenzoyl) adenosine-5′-triphosphate

DRG:

Dorsal root ganglion

FLIPR:

Fluorometric imaging plate reader

FREQ:

Frequency of contractions

HTS:

High throughput screening

IB4:

Isolectin B4

LS:

Lumbosacral

LUT:

Lower urinary tract

LUTS:

Lower urinary tract symptoms

NANC:

Nonadrenergic, noncholinergic

OAB:

Overactive bladder

PPADS:

Pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid

TL:

Thoracolumbar

TNP-ATP:

2′,3′-O-(2,4,6-trinitrophenyl)adenosine-5′-triphosphate

TRPV1:

Transient receptor potential vanilloid-1 receptor

TV:

Threshold volume

UTI:

Urinary tract infection

UTP:

Uridine 5′-triphosphate

α,βmeATP:

α,β-methyleneATP

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Authors and Affiliations

  1. Afferent Pharmaceuticals, 2755 Campus Drive, Suite 100, San Mateo, CA, 94403, USA

    Anthony P. D. W. Ford

  2. Inflammation Disease Biology, Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ, 07110, USA

    Debra A. Cockayne

Authors
  1. Anthony P. D. W. Ford
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  2. Debra A. Cockayne
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Correspondence to Anthony P. D. W. Ford .

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Editors and Affiliations

  1. Wake Forest University, Medical Center Blvd., Winston-Salem, 27157-1088, North Carolina, USA

    Karl-Erik Andersson

  2. Academic Medical Center, Dept. Pharmacology & Pharmacotherapy, University of Amsterdam, Meibergdreef 15, Amsterdam, 1105 AZ, Netherlands

    Martin C. Michel

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© 2011 Springer-Verlag Berlin Heidelberg

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Ford, A.P.D.W., Cockayne, D.A. (2011). ATP and P2X Purinoceptors in Urinary Tract Disorders. In: Andersson, KE., Michel, M. (eds) Urinary Tract. Handbook of Experimental Pharmacology, vol 2011. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16499-6_22

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