Tachykinin receptors of the NK₂ type involved in the acetylcholine release by nicotine in guinea‐pig bladder

Abstract

1 The effects of guanethidine and tachykinins on nicotine-and electrical stimulation-induced cholinoceptor responses were studied in isolated urinary bladder from the guinea-pig. 2 Acetylcholine release and the contractile response stimulated by nicotine were partially reduced by a sympathetic nerve blocker, guanethidine. Neurokinin A (but not substance P methyl ester or senktide) enhanced both acetylcholine release and contraction by nicotine in the presence of guanethidine. 3 Frequency-contraction curves (1 to 50 Hz) for electrical field stimulation (EFS) were partially reduced by atropine (1 gM), and after desensitization to ,-methylene adenosine 5'-triphosphate, the atropine-resistant contraction to EFS was completely abolished. Guanethidine, the tachykinin antagonist [D-Arg', D-Pro2, Trp7'9, Leu"]-substance P and application of neurokinin A or substance P did not change the contractile response to EFS. Preganglionic nerve stimulation (5 Hz and 20 Hz) also evoked a similar response to EFS and was not influenced at all by guanethidine or neurokinin A. 4 We conclude that the ability of nicotine to release acetylcholine is enhanced both by endogenous tachykinins (probably released from sympathetic nerves) and by exogenously applied tachykinins as a result of interaction with NK2 receptors in the urinary bladder.

Effects of Distigmine on Electrical Field Stimulation-Induced Contraction of Mouse Urinary Bladder Smooth Muscles

“…The activity of TTX-sensitive and atropine-resistant contractile components was nearly abolished by α,β-mATP targeting purine P2X receptors; this phenomenon is likely attributable to neurogenic ATP ( fig. 1 ) ings that both neurogenic ACh and ATP contribute to EFS-induced UBSM contractions are similar to those of previous reports describing the characteristics of EFSevoked contractions in mice, guinea pig, and human UB tissues [26,27,[29][30][31] .…”

“…Although ACh is a primary mediator to trigger UB contraction during a micturition reflex, pharmacological studies have shown that adenosine triphosphate (ATP) plays a small but substantial role in electrical field stimulation (EFS)-induced UB contractions [23][24][25][26][27][28][29] . Given the pharmacological characteristics of distigmine, its restorative effects on impaired UB contractile functions are likely produced through the exclusive potentiation of ACh-induced contractile responses of UBSM; however, this has not been shown with functional studies in EFS-evoked UBSM contractions.…”

Local receptors as novel regulators for peripheral clock expression

“…Sustained release of neurotransmitter-like substances occurs in the bladder, analogous to the experimental incubation of the agonists in this study. Acetylcholine and ATP can be released due to nervous activity, and, more notably, non-neuronal activities, such as stretches during normal bladder filling and distension ( 37 , 40 , 41 ), bladder contractions ( 28 , 42 ), spontaneous release ( 28 , 42 – 44 ), and stimulation by inflammatory mediators ( 45 – 50 ) accumulated in the tissue under pathological conditions and during aging. The tonic release of neurotransmitters due to parasympathetic activity during bladder storage may also occur ( 51 , 52 ).…”

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

“…Furthermore disruption of the preprotachychynin gene which encodes for substance P, leads to an impaired response to chemical irritation of the urinary tract in mice (Kiss et al, 2001). Neurokinin A and substance P also have an excitatory effect on autonomic ganglia in the bladder (Kawatani et al, 1989;Shinkai et al, 1993) and on bladder smooth muscle (Maggi, 1997b). Thus Substance P or a related neurokinin may be an excitatory transmitter in bladder afferent pathways in the peripheral and central nervous system.…”