Role of peripheral 5-HT1A receptors in detrusor over activity associated with partial bladder outlet obstruction in female rats.
We have investigated the role of peripheral 5-hydroxytryptamine 1A (5-HT(1A)) receptors and their probable up-regulation in rat model of partial bladder outlet obstruction. Bladder outlet obstruction was induced in adult female rats, hypertropic bladders were harvested after 6 weeks and isometric contractions of bladder strips were recorded. A marked spontaneous activity of the bladder was observed in obstructed bladder strips compared to control strips. The effect of alpha(1A/1D)-adrenergic antagonist, tamsulosin, was observed to be inhibitory on the spontaneous contractions albeit at higher doses (10, 30 and 100 nM). As tamsulosin at higher doses also has high affinity for 5-HT(1A) receptors, the role of peripheral 5-HT(1A) receptors in overactive bladder was hypothesized. 8-hydroxy-2-(di-n-propylamino) tetralin [8-OH-DPAT], a selective 5-HT(1A) receptor agonist, dose-dependently induced significant contractions in the obstructed bladder strips, compared to control bladders. N-[2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide dihydrochloride (WAY-100635), a selective 5-HT(1A) receptor antagonist, competitively antagonized the contractile response to 8-OH-DPAT in obstructed bladder strips in a dose-dependent manner. Tamsulosin at a higher dose was also observed to antagonize the responses to 8-OH-DPAT. Taken together, these observations suggest the involvement of peripheral 5-HT(1A) receptors in detrusor over activity associated with bladder outlet obstruction in female rats.
Mittra
Shivani
S
Department of Pharmacology, NDDR, Ranbaxy Research Laboratories, Plot No 20, Udyog Vihar Industrial Area, Sector 18, Gurgaon-122001, Haryana, India. shivani.mittra@ranbaxy.com
Malhotra
Shivani
S
Naruganahalli
Krishna S
KS
Chugh
Anita
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006984:Hypertrophy; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D000077409:Tamsulosin; D015854:Up-Regulation / Q000502:physiology; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000503:physiopathology*
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011725:Pyridines; D018340:Receptors, Adrenergic, alpha-1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000077409:Tamsulosin