Non-adrenergic And Non-cholinergic Research Articles

Brainstem Neuronal Circuitries Controlling Gastric Tonic and Phasic Contractions: A Review.

This review is on how current knowledge of brainstem control of gastric mechanical function unfolded over nearly four decades from the perspective of our research group. It describes data from a multitude of different types of studies involving retrograde neuronal tracing, microinjection of drugs, whole-cell recordings from rodent brain slices, receptive relaxation reflex, accommodation reflex, c-Fos experiments, immunohistochemical methods, electron microscopy, transgenic mice, optogenetics, and GABAergic signaling. Data obtained indicate the following: (1) nucleus tractus solitarius (NTS)-dorsal motor nucleus of the vagus (DMV) noradrenergic connection is required for reflex control of the fundus; (2) second-order nitrergic neurons in the NTS are also required for reflex control of the fundus; (3) a NTS GABAergic connection is required for reflex control of the antrum; (4) a single DMV efferent pathway is involved in brainstem control of gastric mechanical function under most experimental conditions excluding the accommodation reflex. Dual-vagal effectors controlling cholinergic and non-adrenergic and non-cholinergic (NANC) input to the stomach may be part of the circuitry of this reflex. (5) GABAergic signaling within the NTS via Sst-GABA interneurons determine the basal (resting) state of gastric tone and phasic contractions. (6) For the vagal-vagal reflex to become operational, an endogenous opioid in the NTS is released and the activity of Sst-GABA interneurons is suppressed. From the data, we suggest that the CNS has the capacity to provide region-specific control over the proximal (fundus) and distal (antrum) stomach through engaging phenotypically different efferent inputs to the DMV.

Effects of selenoprotein P on the contraction and relaxation of the airway smooth muscle

Selenoprotein P (SeP) not only represents the major selenoprotein in plasma, but also provides more than 50% of the total plasma selenium. However, there is no report concerning the direct action of selenium or selenium-containing compounds on the contraction and relaxation of the airway smooth muscle. Therefore, we investigated the effects of SeP and sodium selenite (SS) on the indirectly induced contraction and relaxation of the cat bronchi, and gel contraction of cultured bovine tracheal smooth muscle cells (BTSMC) induced by ATP. In the present results, SeP or SS suppressed the amplitude of twitch-like contractions of cat bronchiole without affecting the non-adrenergic and non-cholinergic (NANC) relaxations evoked by electrical field stimulation. SeP also suppressed the ATP-induced gel contraction of BTSMC. These results suggest that SeP suppresses the amplitude of twitch-like contraction of cat bronchiole by acting directly on the bronchiolar smooth muscle.

Mechanisms involved in the nitric oxide-induced vasorelaxation in porcine prostatic small arteries

Benign prostatic hypertrophy has been known to be related with glandular ischemia processes, and nitric oxide (NO) is a potent vasodilator agent. Therefore, the current study investigates the mechanisms underlying the NO-induced vasorelaxation in pig prostatic small arteries. In microvascular myographs, relaxation to electrical field stimulation (EFS), or to exogenous (S)-nitroso-N-acetylpenicillamine (SNAP) and acetylcholine (ACh), was observed on noradrenaline-precontracted prostatic small arterial rings under non-adrenergic and non-cholinergic (NANC) conditions. EFS (1-16Hz) and exogenous SNAP (0.1-30μM) evoked frequency- and concentration-dependent relaxation, respectively. Tetrodotoxin, a neuronal voltage-gated Na(+) channel blocker, abolished the EFS-evoked relaxation. ACh (1nM-10μM) induced concentration-dependent relaxation, which was reduced by the NO synthase inhibitor N(G)-nitro-L: -arginine (L: -NOARG). L: -NOARG also reduced the EFS-elicited relaxation but failed to modify the response to SNAP. 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin (IbTX), blockers of soluble guanylyl cyclase and large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, respectively, reduced EFS-, SNAP-, and ACh-induced relaxation. The combination of ODQ with IbTX did not produce further inhibition of the responses to either SNAP or ACh, compared with ODQ alone. Blockade of cyclooxygenases and intermediate and small conductance Ca(2+)-activated, ATP-dependent, and voltage-gated K(+) channels did not change the EFS and SNAP responses. In conclusion, our results suggest that NO and non-NO non-prostanoid factor(s) derived from NANC nerves are involved in the vasodilatation of pig prostatic small arteries. NO produces relaxation through soluble guanylyl cyclase activation-dependent BK(Ca) channel opening and through guanylyl cyclase-independent mechanisms. The vasodilatation elicited by NO could be useful to prevent prostatic ischemia.

Radioimmunoassay of vasoactive intestinal peptide immunoreactivity in guinea pig respiratory tract

Although vasoactive intestinal peptide (VIP) has been suggested to be the neurotransmitter of non-adrenergic and non-cholinergic (NANC) inhibitory nerves, its physiological functions and movements in the airway are obscure. In this study, VIP immunoreactivity in the respiratory tract from guinea pigs was measured as a preliminary experiment to elucidate its functions. VIP immunoreactivity was measured by radioimmunoassay. The rate of VIP disappearance during extraction was 52.5 +/- 17.4 (mean +/- SD)%. The dose-response curve of tissue extract almost paralleled the standard curve of authentic VIP. VIP immunoreactivity of tracheas was 939.9 +/- 262.1 pg/g wet weight and that of extrapulmonary bronchi was 858.0 +/- 241.1 pg/g wet weight. Although VIP immunoreactivity of lung extracts was not detectable in 14 samples out of 23, the value of 9 samples was 111.7 +/- 61.5 pg/g wet weight. These results suggest that there may be more VIP immunoreactivity present in tracheas and extrapulmonary bronchi than in lungs.

The role of sulfur dioxide as an endogenous gaseous vasoactive factor in synergy with nitric oxide

To explore the physiological role of endogenous gaseous sulfur dioxide (SO 2) on vascular contractility and its underlying cellular and molecular mechanisms, vasodilation experiment of isolated rat thoracic aortic rings by gaseous SO 2 was carried out and the signal transduction pathways involved in the vascular effects of SO 2 were investigated. In the present study, SO 2 gas and SO 2 gas-bubbled solution (SO 2 stock solution) were first used to relax vascular tissues. The results show: (1) Gaseous SO 2 relaxed rat thoracic aortic rings in a dose-dependent manner (from 1 to 2000 μM). The vasorelaxant effect of SO 2 at physiological relevant and low concentrations (<450 μM) was endothelium-dependent, and at high concentrations (>500 μM) was endothelium-independent. (2) The vasorelaxation by addition of SO 2 stock solution (final concentrations ⩽2 mM) was actually caused by SO 2 molecules, not by sulfite or bisulfite, and the characteristic of vasorelaxation by SO 2 was different from that of sulfite and bisulfite. (3) The vasorelaxant effect of SO 2 was not due to the altered neurotransmitter release from the autonomous or nonadrenergic and noncholinergic (NANC) nerve endings, also not due to superoxide and hydrogen peroxide produced in the vascular tissues, also disapproving the involvement of prostaglandin, PKC, β-adrenoceptor and cAMP pathways. (4) The vasorelaxant effect of SO 2 at the physiological relevant and low concentrations was mediated by the cGMP pathway. (5) There was the synergistic effect on smooth muscle relaxation between much lower concentrations of SO 2 (3 μM) and NO (3 or 5 nM). These findings led to the conclusions: endogenous gaseous SO 2 was a vasoactive factor, which might regulate vascular smooth muscle tone in synergy with NO.

Electrically stimulated relaxation is not mediated by GABA in cat lower esophageal sphincter muscle

This study examined the effect of Gamma-Amino butyric acid (GABA) and selective GABA receptor related drugs on the electrically stimulated relaxation in the lower esophageal sphincter muscle (LES) of a cat. Tetrodotoxin (10(-6) M) suppressed the electrically stimulated (0.5-5 Hz) relaxation of the LES. However, guanethidine (10(-6) M) and atropine (10(-6) M) had no effect indicating that the relaxations were neurally mediated via the nonadrenergic and noncholinergic (NANC) pathways. NG-nitro-L-arginine methyl ester (10(-4) M, L-NAME) also inhibited the relaxant response but did not completely abolish the electrically stimulated relaxation with 60 % inhibition, which suggests the involvement of nitric oxide as an inhibitory transmitter. This study examined the role of GABA, an inhibitory neurotransmitter, on neurally mediated LES relaxation. GABA (10(-3)-10(-5) M, non selective receptor agonist), muscimol (10(-3)-10(-5) M, GABA-A agonist), and baclofen (10(-3)-10(-5) M, GABA-B agonist) had no significant effect on the electrically stimulated relaxation. Moreover, bicuculline (10(-5) M, GABA-A antagonist) and phaclofen (10(-5) M, GABA-B antagonist) had no inhibitory effect on the electrically stimulated relaxation. This suggests that GABA and the GABA receptor are not involved in the electrically stimulated NANC relaxation in the cat LES.

Asthma, asthma medication and autonomic nervous system dysfunction.

Asthma is associated with autonomic nervous imbalance: an increased bronchial sensitivity to cholinergic constrictors and possibly a decreased sensitivity to beta2-adrenergic dilators have been reported in this disease. Also, non-adrenergic and non-cholinergic (NANC) mediators have a small regulatory effect on airway function. These mediators contribute to the pathogenesis of asthma not only by regulating smooth muscle tone in the airways but also by affecting pulmonary blood flow, endothelial permeability and airway secretions. In many studies increased parasympathetic responsiveness has been associated with clinical asthma or the worsening of asthma in adults. However, most of the studies in children have not found association between autonomic dysfunction and asthma. Therefore, the autonomic dysfunction in asthma may be related to more advanced disease or long-term asthma medication in adults. This article briefly reviews the relationships between airway inflammation, beta2-agonist, anticholinergic and glucocorticoid medication as well as autonomic nervous function in asthma.

Enzymohistochemical study on burn effect on rat intestinal NOS.

The blood irrigate flow obstruction, especially the gastrointestinal (GI) ischemia[1], is the main factor of the damage to the digestive tract caused by serious burns. The effect of GI ischemia on the whole body is extensive and profound, which not only causes the increase of intestinal permeability and the movement of bacteria and toxin in the intestinal cavity, but releases a large quantity of inflammatory media. Neuroendocrine element after burns is closely related to intestinal damage[2]. As is known at present, abundant nitric oxide synthase (NOS) is distributed in GI tract, whose product NO is a nonadrenergic and noncholinergic (NANC) restraining transmitter in enteric nervous system which participates extensively in various physiological functions in the intestinal tract[3]. Few reports about the effects on intestinal NOS after serious burns are available. We used scalded rat model with degree III 40% of body surface area (TBSA), and enzymatic histological and biochemical methods to observe dynamically the active changes of empty myenteric plexus NOS and changes of jejunal tissue MDA SOD and GSH-PX and probe into the relationship between NOS and intestinal tissue and function damage as well as their mechanism so as to provide morphological experimental basis for clinical treatment.

O óxido nitrico como neurotransmissor no sistema nervoso entérico: fisiopatologia e implicações no íleo adinâmico

Nesta revisão do sistema nervoso entérico, enfatiza-se o mecanismo da inibição não-adrenérgica e não-colinérgica na contratilidade do sistema digestório. Introduz-se a síntese e metabolismo do óxido nítrico com apresentação das sintases do óxido nítrico. Atualiza-se mostrando o óxido nítrico como neurotransmissor do mecanismo inibitório não-adrenérgico e não-colinérgico, demonstrando sua atividade na musculatura lisa gastrointestinal e possível mecanismo intracelular através da cGMP. Após atualização do mecanismo do peristaltismo e do complexo motor migratório, faz-se uma descrição do íleo adinâmico. Por fim, todo raciocínio apresentado condensa-se na fisiopatologia do íleo adinâmico.

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro

The neurotransmitters responsible for neurogenic airway relaxation are still unknown. We investigated the effects of N omega-nitro-L-arginine methylester (L-NAME) on nonadrenergic and noncholinergic (NANC) relaxation evoked by electrical stimulation of vagus nerves in vivo and in vitro in cat. To that end, we measured pulmonary resistance during vagal nerve stimulation (VS) in vivo, and isometric tension of small bronchi (1-3 mm outer diameter) during electrical field stimulation (EFS) in vitro. During infusion of 5-hydroxytryptamine (5-HT), VS transiently decreased total pulmonary resistance in the presence of atropine and propranolol, with peak relaxation at several seconds after the VS and a gradual return to baseline within 2-3 min. L-NAME abolished the initial peak relaxation and reduced the peak amplitude, but did not affect the duration of the NANC relaxation. In small bronchi obtained from control cats, EFS evoked a biphasic NANC relaxation, comprising an initial fast component followed by a second slow component, and L-NAME (10(-5) M) selectively abolished the first component without affecting the second. Whilst in the small bronchi obtained from L-NAME pretreated cats, EFS elicited only the slow component of NANC relaxation, which was insensitive to L-NAME but sensitive to tetrodotoxin. These results indicate that nonadrenergic noncholinergic relaxation induced by vagal nerve stimulation during infusion of 5-hydroxytryptamine can be classified into two components, and that at least two neurotransmitters, including nitric oxide, are involved in the relaxation.

Patterns of electrical activity and neural responses in canine proximal duodenum

The patterns of electrical activity and neural inputs to the proximal duodenum between the pyloric sphincter and the sphincter of Oddi were studied in muscles of the dog. Smooth muscle cells in the most proximal region were electrically quiescent, but slow waves were recorded in all regions distal to the first few millimeters. Electrical activity was recorded from circular muscle cells near the myenteric and submucosal surfaces of the circular layer, and slow wave activity was similar in both regions. The nature of neural inputs was also characterized. With electrical field stimulation, responses in cells near the submucosal surface were predominantly excitatory junction potentials (EJPs); near the myenteric border responses were either inhibitory junction potentials (IJPs) or biphasic responses (i.e., small EJPs followed by IJPs). EJPs were blocked by atropine. IJPs were nonadrenergic and noncholinergic (NANC), and several experiments suggested that nitric oxide (NO), or a NO-releasing compound, serves as the inhibitory neurotransmitter in this region. Exogenous NO caused hyperpolarization of membrane potential. IJPs and the hyperpolarization response to NO were sensitive to apamin. These data describe the myogenic mechanisms and neurogenic apparatus that appear to regulate motility in the most proximal region of the duodenum.

Key roles of nitric oxide and cyclic GMP in nonadrenergic and noncholinergic inhibition in rat ileum

Nonadrenergic and noncholinergic (NANC) inhibitory responses in circular and longitudinal muscles of the rat ileum were studied separately in vitro. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region. Nitro-arginine inhibited the relaxation and L-arginine counteracted the effect of nitro-arginine. Treatment of the preparation with superoxide dismutase (SOD) and methylene blue resulted in enhancement and inhibition, respectively, of the relaxation induced by distension. Nitric oxide caused relaxation of the circular muscle in a dose-dependent manner. 8-Bromo cyclic GMP (cGMP) caused relaxation of the circular muscle. Electrical transmural stimulation caused relaxation followed by a rebound contraction of the longitudinal muscle. Nitro-arginine inhibited the relaxation and L-arginine counteracted this inhibition. Similar results to those in the circular muscle were obtained in the longitudinal muscle with SOD, methylene blue, nitric oxide and 8-bromo cGMP. Electrical field stimulation increased the cGMP content of the longitudinal muscle preparation. Nitric oxide also increased the cGMP content of smooth muscle cells obtained from circular and longitudinal muscles of rat ileum. Preincubation of smooth muscle cells with methylene blue inhibited the effect of nitric oxide on the cGMP content. These results suggest a key role of cGMP in NANC inhibitory responses in rat ileum. The factors mediating the responses are discussed.

Role of nitric oxide in non-adrenergic, non-cholinergic inhibitory junction potentials in canine ileocolonic sphincter.

1. Electrical field stimulation causes neurally-mediated relaxation of the ileocolonic sphincter that is due to activation of non-adrenergic and non-cholinergic (NANC) nerves. Recent studies have suggested that nitric oxide (NO) is the neurotransmitter that mediates relaxation. 2. Using intracellular recording techniques, we have tested whether NANC inhibitory junction potentials (i.j.ps) in the canine ileocolonic sphincter are also mediated by NO. 3. Electrical field stimulation elicited excitatory and inhibitory junction potentials: e.j.ps were blocked by atropine (10(-6) M) and tetrodotoxin (TTX; 10(-6) M); i.j.ps were also blocked by TTX and partially blocked by apamin (10(-6) M). I.j.ps were unaffected by atropine, phentolamine and propranolol (all at 10(-6) M). 4. The arginine analogues, L-NG-nitroarginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), decreased the amplitude of i.j.ps and L-arginine, but not D-arginine, partially restored the i.j.ps. 5. I.j.ps were also inhibited by oxyhaemoglobin (1%), but not by methaemoglobin. 6. Exogenous NO (10(-7) M to 3 x 10(-5) M) caused concentration-dependent hyperpolarizations that were similar in amplitude to the NANC nerve-evoked i.j.ps. Hyperpolarizations to NO were unaffected by L-NAME, but were blocked by oxyhaemoglobin. 7. Tetrodotoxin, L-NAME and oxyhaemoglobin all caused depolarization of resting membrane potential. 8. The specific guanosine 3':5'-cyclic monophosphate phosphodiesterase inhibitor, M&B 22948, caused hyperpolarization, increased the maximum level of hyperpolarization reached during i.j.ps, and increased the duration of i.j.ps. 9. These data further support the hypothesis that NANC neurotransmission in the ileocolonic sphincter is mediated by NO or an NO-releasing compound. The data also suggest that tonic release of NO, possibly from spontaneous firing of NANC nerves, may regulate resting membrane potential and tone in this sphincter.

Nonadrenergic inhibitory nerves attenuate neurally mediated contraction in cat bronchi

Effects of nonadrenergic and noncholinergic (NANC) inhibitory nerves on cholinergic neurotransmission were examined in isolated bronchial segments from cats in the presence of propranolol (10(-6) M) and indomethacin (10(-6) M) by use of electrical field stimulation (EFS) techniques. EFS caused contraction alone in tissues at the baseline tension and biphasic responses (contraction and relaxation) in tissues precontracted with 5-hydroxytryptamine. Contraction was abolished by atropine (10(-6) M), and relaxation was abolished by tetrodotoxin (10(-6) M). At the baseline tension, EFS at frequencies greater than 10 Hz inhibited the subsequent (4 min later) contraction induced by EFS at 1-5 Hz. EFS-induced inhibition was stimulus frequency dependent and reached maximum at 20 Hz. However, EFS at 20 Hz did not inhibit the subsequent contractile response to acetylcholine (10(-7) to 10(-3) M). Exogenously applied vasoactive intestinal peptide mimicked EFS-induced inhibitory effects, but substance P and calcitonin gene-related peptide did not. The inhibitory effect of EFS at 20 Hz was not altered by pyrilamine, cimetidine, naloxone, methysergide, phentolamine, BW755C, AF-DX 116, or removal of epithelium. These results imply that the NANC transmitter acts via presynaptic cholinergic receptors.

モルモット気道ＶＩＰ免疫活性の測定 ＶＩＰ抽出法の基礎的検討

Vasoactive intestinal peptide (VIP) is suggested to be the neurotransmitter of non-adrenergic and non-cholinergic (NANC) inhibitory nerves in the human airway. In this study, we investigated the procedures of VIP extraction from tissues because it was difficult to measure VIP immunoreactivity in lung parenchyma from guinea pigs when frozen tissues were used. With microwave treatment VIP immunoreactivity of the tracheas was 1.29±0.35 (mean±SD) ng/g wet weight and that of the extrapulmonary bronchi was 1.41±0.31 ng/g wet weight.VIP immunoreactivity of the tracheas and the extrapulmonary bronchi was increased significantly with the microwave treatment compared with the case when frozen tissues were used without the microwave treatment. Although VIP immunoreactivity of the lung extract was not detectable in 10 samples out of 13 samples when frozen tissues were used without the microwave treatment, it became possible to be detected in all samples with the microwave treatment. VIP immunoreactivity of the lung from 13 samples was 0.10±0.03 ng/g wet weight. Although VIP immunoreactivity was present more in the tracheas and the extrapulmonary bronchi than in the lungs, the absolute amount of VIP immunoreactivity in the lung parenchyma was considerable.

The relaxing response of the isolated rat duodenum to nicotine

1. 1. The relaxing responses of the atropine-treated isolated rat duodenum to 12 μM nicotine (N) and transmural electrical stimulation (S) have been compared. 2. 2. The effects of both N and S were unaffected by 3–30 μM guanethidine or previous reserpinization (1 mg/kg, i.p. during 5 days). 3. 3. The effects of N and S were completely blocked by 0.5–2.0 mM procaine, 0.1 mM butacaine or 0.3–1.2 μM tetrodotoxin. 4. 4. The relaxing response to N but not that to S was blocked by 0.3 mM hexamethonium or 3 μM mecamylamine and absent in the nicotine-desensitized preparation. 5. 5. The effects of both N and S were unaffected in the adenosine-5′-triphosphate (ATP)-desensitized preparation. 6. 6. It is suggested that the nonadrenergic and noncholinergic (NANC) relaxation of the rat duodenum in response to N and S is also nonpurinergic.

Adrenergic and non-adrenergic, non-cholinergic control of airways.

In addition to cholinergic neural mechanisms, airway tone is influenced by adrenergic mechanisms and by more recently described neural mechanisms which are non-adrenergic and non-cholinergic (NANC). Sympathetic innervation to human airways is very sparse and there is no functional adrenergic innervation of smooth muscle, although sympathetic fibres may supply ganglia, submucosal glands and bronchial vessels. Airway tone may be influenced by circulating adrenaline and there is some evidence that adrenaline secretion may be impaired in asthma. beta-Adrenoceptors (which are almost entirely of the beta 2-subtype) are localized to many cell types in airways and beta-agonist may be beneficial in airway obstruction, not only by directly relaxing airway smooth muscle (from trachea to terminal bronchioles), but by inhibiting mast cell mediator release, by modulating cholinergic nerves, by reducing bronchial oedema and by reversing the defect in mucociliary clearance. There is little evidence that beta-receptor function is impaired in asthma. Alpha-adrenoceptors, which are bronchoconstrictor, may be activated by inflammatory mediators and disease, and alpha-agonists cause bronchoconstriction in asthmatic patients. However, alpha-antagonists have little effect, which questions the role of alpha-receptors in asthma. NANC nerves which relax human airways have been demonstrated in vitro. Although the neurotransmitter is not certain, there is now convincing evidence that it may be vasoactive intestinal peptide (VIP) and a related peptide histidine methionine (PHM). VIP and PHM immuno-active nerves are found in human airways, and both peptides potently relay human airways in vitro (but not in vivo because of diffusion and metabolism problems).(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation of a Peptide Material Showing Strong Rectal Muscle-Contracting Activity from Chicken Rectum and Its Identification as Chicken Neurotensin

A peptide with strong activity to contract isolated whole chick rectum, RC-substance, in an acid-acetone extract prepared from 2.0 kg wet weight of chicken rectums was isolated by gel filtration on Sephadex G-25, ion exchange chromatography on a SP-Sephadex C-25 column, and high voltage paper chromatography. The close purity of this substance was established by high performance liquid chromatography (HPLC). The RC-substance displayed the same pharmacological and enzymatic properties as bovine neurotensin (NT). However, it differed from bovine NT in its behavior during the ion exchange chromatography, in its mobility during the electrophoresis, and in its retention time on HPLC. The amino acid analysis by a conventional OPA method revealed that all ten amino acid residues of which molar ratios were integral were common with those of chicken NT. Its biological activities were equipotent to those of bovine NT, suggesting the presence of proline in the COOH-terminal hexapeptide. From these results, it can be concluded that the RC-substance is identical to chicken NT. Exposure to high concentrations of bovine NT rendered the rectal smooth muscle of the chicken insensitive to subsequent applications of the RC-substance as well as bovine NT. This desensitization also reduced specifically the contractile resonpses of the rectal muscle elicited by non-adrenergic and non-cholinergic (NANC) nerve stimulation, suggesting a possible physiological role of the RC-substance as the neurotransmitter of NANC neurones.

A pharmacological analysis of the responses of the gastrointestinal smooth muscle of the bat to transmural and periarterial nerve stimulation.

A comparative study of the responses of the gastrointestinal tract of the guinea-pig and of the fruit-eating bat Eidolon helvum to transmural nerve stimulation (TNS) was made. The stomach and rectum of the guinea-pig, the bat and the guinea-pig ileum contracted in response to TNS. These contractions were cholinergic in nature because atropine blocked and physostigmine potentiated them. Tetrodotoxin reversibly abolished these contractions suggesting that they were nerve-mediated. The bat isolated ileum usually responded to TNS with mixed motor and inhibitory components. In some cases, there were only motor or inhibitory components. The motor component was abolished by atropine and potentiated by physostigmine. However, the inhibitory component was non-adrenergic and non-cholinergic (NANC). Tetrodotoxin abolished the motor component without influencing the inhibitory components. Periarterial nerve stimulation of the bat ileum produced a relaxation that was blocked by bretylium, propranolol, phentolamine, reserpine and tetrodotoxin. It is concluded that the bat gastrointestinal smooth muscle, like the guinea-pig, has cholinergic excitatory innervation; however, the bat ileum has both a cholinergic excitatory innervation and a nonadrenergic and non-cholinergic inhibitory component.