Nonadrenergic, noncholinergic

Nonadrenergic noncholinergic inhibitory responses to autonomic nerve stimulation are mainly mediated through NO synthesized by nNOS NO plays a crucial role as a neurotransmitter from the peripheral efferent nerves, thus being called nitrergic. This provides a... 

Summation The overall response is the arithmetic sum of the contribution brought by each receptor (e.g., NKX and NK2). Capsaicin-induced contraction of rat isolated urinary bladder, electrical field stimulation (EFS)-induced nonadrenergic, noncholinergic contraction of the isolated guinea pig bronchus or renal pelvis when SP metabolism is blocked by peptidase inhibitors are all examples of summation. Both NK and NK2r antagonists are required to abolish such kind of response, but each antagonist substantially reduces the response... 

Specialization Each receptor contributes to morphologically (e.g., phasic vs. tonic) or temporally (early vs. late) distinct components of the overall response. This is the case of prolonged EFS-induced nonadrenergic, noncholinergic contraction the guinea pig colon or rat urinary bladder, where the fast and late components of the contraction are mediated by NKxror NK2r, respectively... 

Supra-additivity This is a special case of cooperation where the blockade of a single receptor is not sufficient to reduce the overall response. Capsaicin-induced nonadrenergic, noncholinergic contraction in the guinea pig ileum or common bile duct can be inhibited only when at least two different TK receptors are blocked (e.g., NKX + NK2, NKX + NK3, NK2 + NK3)... 

Mitchell, J. A., Sheng, H., Forstermann, U., and Murad, F. (1991). Characterization of nitric oxide synthases in nonadrenergic noncholinergic nerve containing tissue from the rat anococcygeus muscle. Br. J. Pharmacol. 104, 289-291. 

Tucker, J. F., Brave, S. R., Charalambous, L., Hobbs, A. J., and Gibson, A. (1990). L-N - -nitro-arginine inhibits nonadrenergic, noncholinergic relaxations of guinea pig isolated tracheal smooth muscle. Br. J. Pharmacol. 100, 663-664. 

Table 6-1 Some of the Transmitter Substances Found in Autonomic Nervous System (ANS), Enteric Nervous System (ENS), and Nonadrenergic, Noncholinergic Neurons.1...

As previously noted, the vesicles of both cholinergic and adrenergic nerves contain other substances in addition to the primary transmitter. Some of the substances identified to date are listed in Table 6-1. Many of these substances are also primary transmitters in the nonadrenergic, noncholinergic nerves described in the text that follows. They appear to play several roles in the function of nerves that release acetylcholine or norepinephrine. In some cases, they provide a faster or slower action to supplement or modulate the effects of the primary transmitter. They also participate in feedback inhibition of the same and nearby nerve terminals. 

The sensory fibers in the nonadrenergic, noncholinergic systems are probably better termed "sensory-efferent" or "sensory-local effector" fibers because, when activated by a sensory input, they are capable of releasing transmitter peptides from the sensory ending itself, from local axon branches, and from collaterals that terminate in the autonomic ganglia. These peptides are potent agonists in many autonomic effector tissues. 

NT = neurotransmitter NANC = nonadrenergic, noncholinergic ACh = acetylcholine SP = substance P 4- = decrease t = increase. 

Ichinose, M., Barnes, P.J., 1989a. Histamine H3-receptors modulate nonadrenergic noncholinergic neural bronchoconstriction in guinea-pig in vivo. Eur. J.Pharmacol. 174, 49-55. 

It is still uncertain whether all of these nonadrenergic, noncholinergic substances are true neurotransmitters. They may act as cotransmitters that are... 

Erection occurs when adrenergic-induced sinusoid tone is antagonized by sacral parasympathetic stimulation that produces sinusoidal relaxation primarily by synthesis and release of the nonadrenergic-noncholinergic (NANC) neurotransmitter nitric oxide (NO). The contribution of acetylcholine-dependent release of NO from the vascular endothelium is uncertain. In vitro electrical stimulation of isolated corpus cavemosum strips (with or without endothelium) produces sinusoidal relaxation by release of neurotransmitters within nerve terminals that is resistant to adrenergic and cholinergic blockers. Inhibitors of the synthesis of NO or of guanosine monophosphate (GMP),... 

The enteric system in the gut wall (Figure 6-2) is the most extensively studied system containing nonadrenergic, noncholinergic neurons in addition to cholinergic and adrenergic fibers. In the small intestine, for example, these neurons contain one or more of the following nitric oxide synthase,... 

In contrast, noradrenergic sympathetic innervation of the airways is sparse, and these fibers do not appear to play a major role in controlling airway diameter. Bronchodilation may be brought about by nonadrenergic, noncholinergic nerves releasing nitric oxide since nitric oxide synthase inhibitors have been shown to reduce bronchodilation produced by electrical field stimulation in vitro. 

Sanders KM, Ward SM, Thornbury KD, Dalziel HH, West-fall DP, Carl A. Nitric-oxide as a nonadrenergic, noncholinergic neurotransmitter in the gastrointestinal-tract. Jpn. J. Pharmacol. 1992 58 220-225. 

Potential sources of NO in the lungs include activated alveolar macrophages, neutrophils alveolar type II cells endothelial cells and airway cells. nNOS is localized to nonadrenergic/noncholinergic nerve terminals and is present in human airway epithelial cells. eNOS is localized to human pulmonary epithelium and bronchial epithelium. Studies have suggested that iNOS is constitutively expressed in human upper airway epithelium... 

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