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The effect of clonidine on the response to stimulation of non‐adrenergic non‐cholinergic nerves in the guinea‐pig urinary bladder in‐vitro

The effects of clonidine on the response of the guinea‐pig urinary bladder detrusor muscle to stimulation of non‐adrenergic non‐cholinergic (NANC) nerves were investigated in‐vitro. In tissues from both treated and chemically sympathectomized animals, in the presence of atropine (10−5 M) to inhibit cholinergic responses, clonidine (10−10‐10−6 M) invariably enhanced the contractile response to NANC nerve stimulation at 2, 5, 10 and 20 Hz. The enhancement was not inhibited by yohimbine (10−5 M), phentolamine (10−5 M), or the histamine H1 or H2‐receptor antagonists mepyramine (10−6 M) or cimetidine (10−5 M) respectively. Phentolamine (10−5 M), like clonidine, enhanced the response to stimulation of NANC nerves at 2, 5, 10 and 20 Hz. Xylazine, another α2‐agonist, which, unlike both clonidine and phentolamine, is not a substituted 2‐imidazoline compound, failed to enhance the response in the bladder to NANC nerve stimulation. The results suggest that clonidine enhances the response to NANC nerve stimulation, independently of its effects on α‐adrenoceptors, by increasing the amount of NANC transmitter available.