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  • 1
    Electronic Resource
    Electronic Resource
    THE ENTERIC NERVOUS SYSTEM AND REGULATION OF INTESTINAL MOTILITY (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 61 (1999), S. 117-142 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract The enteric nervous system exerts local control over mixing and propulsive movements in the small intestine. When digestion is in progress, intrinsic primary afferent neurons (IPANs) are activated by the contents of the intestine. The IPANs that have been physiologically characterized are in the intrinsic myenteric ganglia. They are numerous, about 650/mm length of small intestine in the guinea pig, and communicate with each other through slow excitatory transmission to form self-reinforcing assemblies. High proportions of these neurons respond to chemicals in the lumen or to tension in the muscle; physiological stimuli activate assemblies of hundreds or thousands of IPANs. The IPANs make direct connections with muscle motor neurons and with ascending and descending interneurons. The circular muscle contracts as an annulus, about 2-3 mm in minimum oral-to-anal extent in the guinea pig small intestine. The smooth muscle cells form an electrical syncytium that is innervated by about 300 excitatory and 400 inhibitory motor neurons per mm length. The intrinsic nerve circuits that control mixing and propulsion in the small intestine are now known, but it remains to be determined how they are programmed to generate the motility patterns that are observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.physiol.61.1.117
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  • 2
    Electronic Resource
    Electronic Resource
    Electrophysiological analysis of the actions of pituitary adenylyl cyclase activating peptide in the taenia of the guinea-pig caecum (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 538-544 
    Details
    ISSN: 1432-1912
    Keywords: Pituitary adenylyl cyclase activating peptide (PACAP) ; Taenia caeci ; Electrophysiology Enteric nervous system ; Inhibitory neurotransmitter ; Smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The actions of pituitary adenylyl cyclase activating peptide (PACAP) on membrane potential and conductance were investigated in the taenia of the guinea-pig caecum. The possible role of PACAP in inhibitory transmission was also investigated. Membrane potentials of smooth muscle cells were measured by intracellular microelectrodes, in the presence of hyoscine and nifidepine (both 10−6M). To determine conductance changes, current was passed from external plate electrodes using the technique of Abe and Tomita (1968). PACAP-27 caused a concentration dependent hyperpolarization of the muscle with a maximum of 12–15 mV at 10−6M. The hyperpolarization caused by PACAP was associated with a substantial increase in membrane conductance. The hyperpolarization was abolished by apamin (10−6M), a blocker of small conductance, calcium-dependent, potassium channels, and was reduced to about 50% by suramin (10−4M), which is an antagonist of P2 receptors for purines. The hyperpolarization was not reduced by tetrodotoxin (2 × 10−6M), suggesting PACAP acts directly on the muscle. With continued exposure to PACAP, the hyperpolarization decayed back to resting membrane potential after several minutes, possibly due to receptor desensitization. Inhibitory junction potentials (IJPs) were markedly reduced in amplitude in the period of presumed receptor desensitization to PACAP, were abolished by tetrodotoxin, but were not affected by suramin. Apamin abolished the UP and revealed a small excitatory junction potential. This study implies that PACAP released from nerve fibres in the taenia caeci hyperpolarizes the muscle via an opening of apamin-sensitive potassium channels. The action is probably through type I PACAP receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169388
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  • 3
    Electronic Resource
    Electronic Resource
    Electrophysiological analysis of the actions of pituitary adenylyl cyclase activating peptide in the taenia of the guinea-pig caecum (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 538-544 
    Details
    ISSN: 1432-1912
    Keywords: Key words Pituitary adenylyl cyclase activating peptide (PACAP) ; Taenia caeci ; Electrophysiology ; Enteric nervous system ; Inhibitory neurotransmitter ; Smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The actions of pituitary adenylyl cyclase activating peptide (PACAP) on membrane potential and conductance were investigated in the taenia of the guinea-pig caecum. The possible role of PACAP in inhibitory transmission was also investigated. Membrane potentials of smooth muscle cells were measured by intracellular microelectrodes, in the presence of hyoscine and nifidepine (both 10-6M). To determine conductance changes, current was passed from external plate electrodes using the technique of Abe and Tomita (1968). PACAP-27 caused a concentration dependent hyperpolarization of the muscle with a maximum of 12–15 mV at 10-6M. The hyperpolarization caused by PACAP was associated with a substantial increase in membrane conductance. The hyperpolarization was abolished by apamin (10-6M), a blocker of small conductance, calcium-dependent, potassium channels, and was reduced to about 50% by suramin (10-4M), which is an antagonist of P2 receptors for purines. The hyperpolarization was not reduced by tetrodotoxin (2×10-6M), suggesting PACAP acts directly on the muscle. With continued exposure to PACAP, the hyperpolarization decayed back to resting membrane potential after several minutes, possibly due to receptor desensitization. Inhibitory junction potentials (IJPs) were markedly reduced in amplitude in the period of presumed receptor desensitization to PACAP, were abolished by tetrodotoxin, but were not affected by suramin. Apamin abolished the IJP and revealed a small excitatory junction potential. This study implies that PACAP released from nerve fibres in the taeniacaeci hyperpolarizes the muscle via an opening of apamin-sensitive potassium channels. The action is probably through type I PACAP receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169388
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  • 4
    Electronic Resource
    Electronic Resource
    Nitric oxide synthase is localized predominantly in the Golgi apparatus and cytoplasmic vesicles of vascular endothelial cells (1995)
    Springer
    Histochemistry and cell biology 103 (1995), S. 221-225 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The localization of nitric oxide synthase (NOS) in vascular endothelial cells of submucosal blood vessels from the guinea-pig ileum was examined using NADPH diaphorase histochemistry at the light microscopic level, and endothelial NOS immunohistochemistry at the light and electron microscopic level. The pattern of staining observed following NADPH diaphorase histochemistry and endothelial NOS immunohistochemistry was identical. Endothelial cells of the arterioles, capillaries and venules showed small patches of intense, perinuclear staining. Under the electron microscope, endothelial NOS immunoreactivity was found predominantly in association with the Golgi apparatus and with the membranes of some vesicles. Small regions of the plasma membrane and the rough endoplasmic reticulum also showed some immunoreactivity. The presence of NOS in the Golgi apparatus and in vesicles raises the possibility that NOS may be exteriorized by endothelial cells, and hence that nitric oxide is synthesized extracellularly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01454027
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  • 5
    Electronic Resource
    Electronic Resource
    Activation of neurokinin 1 receptors on interstitial cells of Cajal of the guinea-pig small intestine by substance P (1998)
    Springer
    Histochemistry and cell biology 110 (1998), S. 263-271 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The aims of this work were to determine whether cells that are similar to the interstitial cells of Cajal (ICC) and have immunoreactivity for the neurokinin 1 (NK1) receptor are indeed ICC; to determine whether the agonist, substance P, binds to and activates the receptor on presumptive ICC; and to investigate the relationship between substance P-immunoreactive nerve fibres and ICC. ICC at the level of the myenteric plexus and in the deep muscular plexus in the duodenum and ileum of the guinea-pig were investigated. Immunoreactivities for the ICC marker, Kit, and the NK1 receptor were colocalised in ICC of the myenteric and deep muscular plexuses. In tissue fixed immediately after its removal from the animal, NK1 receptor-immunoreactive ICC were found at the level of the myenteric plexus in the duodenum, but not in the ileum, and in the deep muscular plexus in the duodenum and ileum. The majority of receptor immunoreactivity was on the cell surface. ICC were exposed to substance P (10–7 M), initially at 4°C for 1 h to allow the agonist to bind, followed by incubation at 37°C to allow receptor internalisation to proceed. Exposure to substance P caused the NK1 receptor immunoreactivity to aggregate in clumps in the cytoplasm of ICC of the myenteric and deep muscular plexuses, including the ICC of the myenteric plexus of the ileum, where NK1 receptor immunoreactivity was not seen if tissue was not exposed to substance P. Substance P, to which the fluorescent label, cyanine 3.18 (Cy-3), was coupled, bound to the ICC. The Cy-3-substance P was internalised with the receptor following warming to 37°C. Many, but not all, ICC were closely apposed by nerve fibres with immunoreactivity for substance P. It is concluded that the NK1 receptor immunoreactivity on ICC represents receptor that is functional in the sense that it binds the natural agonist substance P and undergoes agonist-induced internalisation. ICC are likely to receive excitatory innervation from the close approaches of tachykinin-containing nerve fibres.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004180050288
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  • 6
    Electronic Resource
    Electronic Resource
    Analysis of connections between nitric oxide synthase neurons in the myenteric plexus of the guinea-pig small intestine (1995)
    Springer
    Journal of neurocytology 24 (1995), S. 257-263 
    Details
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the myenteric plexus of the guinea-pig ileum, a sub-population of descending interneurons contains nitric oxide synthase. Final neurons in descending motility pathways, inhibitory circular muscle motor neurons, also contain nitric oxide synthase. In this study we used ultrastructural immunocytochemistry to determine whether nitric oxide synthase descending interneurons provide inputs to all nitric oxide synthase neurons. The presence of nitric oxide synthase inputs to 35 nitric oxide synthase nerve cells from three animals was examined. Nine nerve cells from one ganglion were studied in serial section. Every nerve cell received inputs (close contacts and synapses) from nitric oxide synthase terminals. The number of inputs to the nine serially sectioned neurons ranged from 13 to 45. The inputs were found in about equal numbers on the cell bodies and the dendrites. There was no significant correlation between the size of nitric oxide synthase neurons and the number of nitric oxide synthase inputs they received. There was also no correlation between the number of nitric oxide synthase inputs and the number of 5-hydroxytryptamine inputs (determined in a previous study) received by nitric oxide synthase neurons. Random sections through an additional 26 nitric oxide synthase neurons (seven in the same ganglion and 19 from another two myenteric ganglia from different animals) were examined and nitric oxide synthase synapses and close contacts were observed on each neuron. Nitric oxide synthase interneurons and motor neurons are morphologically indistinguishable. However, since all nitric oxide synthase neurons that were examined received inputs from nitric oxide synthase terminals, the nitric oxide synthase descending interneurons appear to provide inputs to both the nitric oxide synthase inhibitory motor neurons and descending interneurons. Hence the nitric oxide synthase descending interneurons are likely to play a direct role in descending motility reflexes, although nitric oxide does not appear to be the primary transmitter at neuro-neuronal synapses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01186538
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  • 7
    Electronic Resource
    Electronic Resource
    Distribution of pituitary adenylyl cyclase activating peptide (PACAP) immunoreactivity in neurons of the guinea-pig digestive tract and their projections in the ileum and colon (1995)
    Springer
    Cell & tissue research 279 (1995), S. 385-392 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Pituitary adenylyl cyclase activating peptide (PACAP) ; Small intestine ; Large intestine ;  Enteric nervous system ; Dorsal root ganglia ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Pituitary adenylyl cyclase activating peptide (PACAP) is a novel hypothalamic peptide that is widely distributed in neurons, including those of the gastrointestinal tract. In this study, a polyclonal antiserum directed against PACAP-27 was used to investigate the localisation of PACAP throughout the gut and to determine the projections of PACAP-immunoreactive (IR) neurons in the guinea-pig small and large intestines. PACAP-IR fibres were seen in the myenteric and submucous plexuses, in the longitudinal and circular muscle layers and around blood vessels of the submucosa throughout the gut. In both the small and large intestine, PACAP-IR cell bodies, most with Dogiel type-I morphology, were seen in the myenteric ganglia following colchicine treatment. Lesion studies (myotomy and myectomy operations) revealed that PACAP-IR interneurons projected anally in the ileum and colon. Myectomy operations resulted in a loss of PACAP-IR fibres in the circular muscle under the operation, whereas PACAP-IR fibres remained in the submucosa and around blood vessels. Following extrinsic denervation of the ileum, the number of PACAP-IR fibres in the submucosal ganglia and around blood vessels decreased. This suggests that a portion of PACAP-IR fibres supplying the submucosal ganglia and blood vessels have an extrinsic source. To investigate this, immunohistochemical studies were performed on sympathetic and dorsal root ganglia. Numerous reactive cells were seen in the dorsal root ganglia, but none was seen in sympathetic pre- or paravertebral ganglia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050295
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  • 8
    Electronic Resource
    Electronic Resource
    Do vasoactive intestinal peptide (VIP)- and nitric oxide synthase-immunoreactive terminals synapse exclusively with VIP cell bodies in the submucous plexus of the guinea-pig ileum? (1995)
    Springer
    Cell & tissue research 281 (1995), S. 485-491 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Nitric oxide synthase ; Vasoactive intestinal peptide ; Immunohistochemistry ; Electron microscopy ; Submucous plexus ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. In the submucous plexus of the guinea-pig ileum, previous light-microscopic studies have revealed that vasoactive intestinal peptide (VIP)-immunoreactive and nitric oxide synthase (NOS)-immunoreactive terminals are found predominantly in association with VIP-immunoreactive nerve cell bodies. In this study, double-label immunohistochemistry at the light-microscopic level demonstrated co-localization of NOS-immunoreactivity and VIP-immunoreactivity in axon terminals in submucous ganglia. About 90% of nerve fibres with NOS-immunoreactivity or VIP-immunoreactivity were immunoreactive for both antigens; only about 10% of labelled varicosities contained only NOS-immunoreactivity or VIP-immunoreactivity. The VIP/NOS varicosities were more often seen in the central parts of the ganglia, close to the VIP-immunoreactive cell bodies. Ultrastructural immunocytochemistry with antibodies to VIP was used to determine if NOS/VIP terminals synapse exclusively with VIP-immunoreactive nerve cell bodies. We examined the targets of VIP-immunoreactive boutons in two submucous ganglia from different animals. Serial ultrathin sections were taken through the ganglia after they had been processed for VIP immunocytochemistry. For each cell body, the number of VIP inputs (synapses and close contacts) was determined. The number of VIP-immunoreactive synapses received by the cell bodies of submucous neurons varied from 0–4 and the number of VIP-immunoreactive close contacts varied from 3–10. There was no significant difference between VIP-immunoreactive nerve cell bodies and non-VIP nerve cell bodies in the number of VIP-immunoreactive synapses and close contacts they received. Thus, the implication from light microscopy that NOS/VIP terminals end predominantly on VIP nerve cells was not vindicated by electron microscopy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050443
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  • 9
    Electronic Resource
    Electronic Resource
    Sources of inputs to longitudinal muscle motor neurons and ascending interneurons in the guinea-pig small intestine (1995)
    Springer
    Cell & tissue research 280 (1995), S. 549-560 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Enteric nervous system ; Immunocytochemistry ; Calretinin ; Calbindin ; Bombesin ; Small intestine ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Light- and electron-microscopic studies were used to investigate connections between specific subgroups of neurons in the myenteric plexus of the guinea-pig small intestine. Inputs to two classes of calretinin-immunoreactive (IR) nerve cells, longitudinal muscle motor neurons and ascending interneurons, were examined. Inputs from calbindin-IR primary sensory neurons and from three classes of descending interneurons were studied. Electron-microscopic analysis showed that calbindin-IR axons formed two types of inputs, synapses and close contacts, on calretinin-IR neurons. About 40% of inputs to the longitudinal muscle motor neurons and 70% to ascending interneurons were calbindin-IR. Approximately 50% of longitudinal muscle motor neurons were surrounded by bombesin-IR dense pericellular baskets and 40% by closely apposed varicosities. At the electron-microscope level, the bombesin-IR varicosities were found to form synapses and close contacts with the motor neurons. Dense pericellular baskets with bombesin-IR surrounded 36% of all ascending interneurons, and a further 17% had closely apposed varicosities. Somatostatin- and 5-HT-IR descending interneurons provided no dense pericellular baskets to calretinin-IR nerve cells. Thus, calretinin-IR, longitudinal muscle motor neurons and ascending interneurons receive direct synaptic inputs from intrinsic primary sensory neurons and from non-cholinergic, bombesin-IR, descending interneurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318359
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  • 10
    Electronic Resource
    Electronic Resource
    Calretinin immunoreactivity of motor neurons in the guinea-pig distal colon and taenia coli (1996)
    Springer
    Cell & tissue research 284 (1996), S. 367-372 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Calretinin ; Calcium-binding protein ; Enteric nervous system ; Distal colon ; Taenia coli ; Vasoactive intestinal peptide (VIP) ; Substance P ; γ-Aminobutyric acid (GABA) ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Calretinin is a calcium-binding protein which occurs in neurons and endocrine cells, including neurons throughout the gastrointestinal tract. Calretinin-immunoreactive (IR) neurons innervate the circular muscle in the guinea-pig distal colon and have descending as well as ascending projections. This suggests that calretinin-IR is in motor neurons, but whether it might be in excitatory or inhibitory motor neurons or both was previously undetermined. The presence of calretinin-IR in neurons innervating the taenia coli has not been previously reported. Numerous fibres in the circular muscle of the distal colon and in the taenia coli displayed immunoreactivity for calretinin. Tachykinin (TK), vasoactive intestinal peptide (VIP), calretinin, and γ-aminobutyric acid (GABA) immunoreactivity was also in fibres innervating these targets. The abundances of these fibres was estimated to be TK〉VIP〉calretinin〉GABA. Double label immunohistochemistry revealed the presence in both tissues of populations of calretinin-IR fibres which were also TK-IR, and fibres with calretinin and GABA-IR in the colon, but calretinin-IR fibres were never VIP-IR. TK- and VIP-IR were in separate populations of nerve fibres as were GABA- and TK-IR. It is concluded that calretinin-IR does not provide a definitive labelling of a physiologically known subgroup of motor neurons, either in the distal colon or in the taenia coli, but that calretinin is most likely to be in excitatory motor neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050597
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