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Modulation of autonomous contractile activity in the isolated whole bladder of the guinea pig
Author(s) -
Gillespie J.I.
Publication year - 2004
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2003.04624.x
Subject(s) - muscarinic acetylcholine receptor , chemistry , substance p , agonist , stimulation , detrusor muscle , parasympatholytic , guinea pig , alpha (finance) , urinary bladder , muscarinic agonist , in vivo , endocrinology , medicine , receptor , biochemistry , biology , neuropeptide , construct validity , nursing , patient satisfaction , microbiology and biotechnology
The over active bladder and bladder outlet obstruction represent clinically significant problems. The first two papers of this month's Scientific Discovery section addresses novel and exiting theories in this field. They also describe new models to investigate these complicated in vivo problems. Professor Gillespie describes that in addition to the neurogenic and myogenic hypothesis bladder over activity is a consequence of inappropriate activation or modulation of phasic activity: the autonomous bladder hypothesis. In his second paper he describes that noradrenaline inhibits autonomous activity in the isolated guinea pig bladder. Both papers add important information on the cellular mechanisms of bladder dysfunction. OBJECTIVE To investigate the actions of the nonhydrolysable analogue of ATP, α,β‐methylene ATP (α,β‐MATP) and the sensory peptide, substance P, on the phasic activity generated by muscarinic stimulation in the isolated whole bladder. Isolated bladder can generate complex contractions resulting in phasic rises in intravesical pressure (the autonomous bladder): activity thought to underlie nonmicturition activity in vivo and which may be important in generating bladder sensations. MATERIALS AND METHODS Experiments were conducted on whole isolated bladders from female guinea pigs (270–300 g). Bladders were cannulated via the urethra, suspended in a heated chamber containing oxygenated solution at 33–36 °C and intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface of the bladder. RESULTS When α,β‐MATP (30–3000 nmol/L) or substance P (30–300 nmol/L) was added to resting bladders there were small rises in intravesical pressure (<2 cmH 2 O). However, in the presence of phasic activity generated by exposing the bladder to the muscarinic agonist arecaidine (100–300 nmol/L) or the nicotinic ligand lobeline (10–30 µmol/L) similar or lower concentrations of α,β‐MATP or substance P produced more dramatic effects: α,β‐MATP and substance P (both at 100 nmol/L) activated a rise in basal pressure of > 15 cmH 2 O and increased the frequency of the phasic activity. On removing α,β‐MATP or substance P, there was a slowing of phasic activity indicative of an inhibitory mechanism. CONCLUSION In addition to direct effects on smooth muscle the agonists α,β‐MATP and substance P appear to be potent regulators of the mechanisms generating phasic activity. A developing concept is that the mechanisms responsible for generating phasic activity underlie nonmicturition activity are the target for excitatory and inhibitory inputs. Regulating such activity may be a factor in generating or modifying bladder sensation. Inappropriate or exaggerated phasic activity could underpin the pathological changes which cause the overactive bladder, thus adding another hypothesis to the neurogenic and myogenic hypotheses of bladder overactivity, i.e. that of the autonomous bladder.