Mechanism of action of nicotine in isolated urinary bladder of guinea‐pig

Abstract

1 Nicotine produced a transient contraction of isolated strips of guinea-pig urinary bladder. The response to nicotine was antagonized by the nicotinic receptor antagonist, hexamethonium but was insensitive to tetrodotoxin.2 The nicotine-induced contraction was potentiated by the cholinesterase inhibitor, physostigmine, and was reduced to 50% and 70% by the muscarinic cholinoceptor antagonist, atropine and the sympathetic neurone blocking drug, guanethidine, respectively. Chemical denervation with 6-hydroxydopamine abolished the inhibitory effect of guanethidine. Simultaneous treatment with atropine and guanethidine did not abolish the response to nicotine, but the degree of inhibition was comparable to that obtained with atropine alone.3 The nicotine-induced contraction was insensitive to bunazosin and yohimbine (al-and Cc2-adrenoceptor antagonists, respectively), and exogenously applied noradrenaline did not cause a contraction even in the presence of blockade of noradrenaline uptake mechanisms with desipramine and normetanephrine and of fi-adrenoceptors with propranolol, suggesting a non-adrenergic nature of the sympathomimetic effect of nicotine in this tissue. 4 The nicotine-induced contraction in the presence of atropine was abolished after desensitization of P2-purinoceptors with a, ,B-methylene adenosine 5'-triphosphate, a slowly degradable ATP analogue selective for P2-purinoceptors. By this desensitization, the response to ATP, but not to histamine, was also abolished.5 A cyclo-oxygenase inhibitor flurbiprofen partially inhibited the nicotine-induced contraction. The degree of the inhibition was more pronounced in the presence of atropine than in its absence. Flurbiprofen antagonized the response to exogenously applied ATP in an unsurmountable manner, but not that to carbachol.6 The present results suggest that nicotine might induce a contraction through an interaction with nicotinic receptors located on the terminals of, possibly, (i) parasympathetic cholinergic, (ii) sympathetic non-adrenergic and (iii) non-sympathetic purinergic nerves in guinea-pig detrusor preparations, and that a portion of the contraction due to the purine nucleotide released is possibly potentiated by intramural prostaglandin(s). Parasympathetic cholinergic output might be modulated by an unknown excitatory substance released by nicotine from sympathetic nerve.7 Nicotine reveals a latent excitatory effect of the sympathetic hypogastric nerve which innervates guinea-pig detrusor.

Differential effects of TAK-802, a selective acetylcholinesterase inhibitor, and carbamate acetylcholinesterase inhibitors on contraction of the detrusor smooth muscle of the guinea pig

“…The concentration of nicotine required for a 50% contractile response was 51 (31-86) AM. Consistent with previous observations (Hisayama et al, 1988), the nicotine-induced contractions were reduced by pretreatment with atropine or hexamethonium, a ganglionic nicotinic antagonist (preliminary observation, N = 3), indicating that nicotine stimulated the intramural parasympathetic ganglion cells to induce the release of ACh from the post-ganglionic nerve terminals, although it has been reported that intramural ganglion cells are not so abundant in the guinea pig bladder (Gabella, 1990). We chose a nicotine concentration of 100 AM to investigate the effects of the AChE inhibitors in this study.…”

Association of Smoking with Urgency in Older People

“…One mechanism to explain the association of current smoking with urgency could be nicotine, which has been shown to produce phasic contraction of the urinary bladder in animal models [30, 31]. Another suggestion for the association could be the effect of ischaemia caused by smoking on detrusor function [32].…”

In vitro Effect of Amikacin on Rat and Human Detrusor Muscle Contraction

“…Nicotine determines contraction through activation of nicotinic receptors of the parasympathetic neurons in parasympathetic ganglia, that are known to be present within the bladder wall [1] . Moreover, nicotinic receptors are located on other nerve terminals and modulate exocytosis of neurotransmitters acting on detrusor contractile function [16] ; this could explain the dose-dependent contractile response to nicotine of rat detrusor, which is reported to be poor of intramural ganglia [17] .…”