Physiological role of neuropeptide Y in the regulation of the ascending phase of the peristaltic reflex

2003 ◽  
Vol 285 (6) ◽  
pp. G1139-G1146 ◽  
Author(s):  
John R. Grider ◽  
Lea E. Langdon
Keyword(s):  
Neuropeptide Y ◽  
Neurotransmitter Release ◽  
Receptor Agonist ◽  
Mechanical Response ◽  
Physiological Role ◽  
Rat Colon ◽  
Inhibitory Influence ◽  
Muscle Stretch ◽  
Peristaltic Reflex

The physiological role of neuropeptide Y (NPY) and of specific NPY receptors in regulating the intestinal peristaltic reflex was examined in three-compartment flat-sheet preparations of rat colon. Graded muscle stretch or mucosal stimulation applied to the central compartment inhibited NPY release in the orad compartment where ascending contraction was measured. NPY and the Y1-receptor agonist [Leu31, Pro34]NPY inhibited, whereas the selective Y1-receptor antagonist BIBP 3226 augmented ascending contraction and substance P (SP) release in the orad compartment induced by muscle stretch or mucosal stimulation. Neither agonist nor antagonist had any effect on descending relaxation or VIP release in the caudad compartment. The Y2-receptor agonist NPY13-36 and antagonist BIIE 0246 had no effect on peptide release or mechanical response. The results indicate that suppression of a tonic inhibitory influence of NPY neurons on excitatory neurotransmitter release contributes substantially to the orad contractile phase of the peristaltic reflex. The effect of NPY on neurotransmitter release is mediated by Y1 receptors.

5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4/5-HT1p receptors on sensory CGRP neurons

1996 ◽  
Vol 270 (5) ◽  
pp. G778-G782 ◽  
Author(s):  
J. R. Grider ◽  
J. F. Kuemmerle ◽  
J. G. Jin
Keyword(s):  
Circular Muscle ◽  
Central Compartment ◽  
Rat Colon ◽  
Muscle Stretch ◽  
Peristaltic Reflex ◽  
Sensory Transmission ◽  
Cgrp Release ◽  
Calcitonin Gene ◽  
Separate Measurement

The intestinal peristaltic reflex can be elicited by mucosal stimulation or circular muscle stretch. Muscle stretch activates extrinsic, whereas mucosal stimulation activates intrinsic calcitonin gene-related peptide (CGRP)-containing sensory neurons. The present study examined the role of 5-hydroxytryptamine (5-HT) in sensory transmission. A three-compartment preparation of rat colon was used that enables separate measurement of sensory transmitters and modulators. Mucosal stimuli (2-8 brush strokes) caused concurrent increase in 5-HT and CGRP release in proportion to the intensity of stimulation. Release of both 5-HT and CGRP occurred exclusively into the central compartment where the stimuli were applied. Exogenous 5-HT caused a concentration-dependent release of CGRP. Release of CGRP induced by exogenous 5-HT or mucosal stimulation was inhibited by selective 5-HT4 and 5-HT1p antagonists but was not affected by 5-HT1A, 5-HT2, and 5-HT3 antagonists. Ascending contraction and descending relaxation of circular muscle measured in the peripheral orad and caudad compartments, respectively, were also selectively inhibited by 5-HT4 and 5-HT1p antagonists added to the central but not peripheral compartments. In contrast, muscle stretch elicited CGRP but not 5-HT release; the ascending contraction and descending relaxation components of the peristaltic reflex induced by muscle stretch were not affected by 5-HT antagonists. We conclude that 5-HT released by mucosal stimulation initiates the peristaltic reflex by activating 5-HT4/5-HT1p receptors on sensory CGRP-containing neurons.

Gastrin-releasing peptide is a modulatory neurotransmitter of the descending phase of the peristaltic reflex

2004 ◽  
Vol 287 (6) ◽  
pp. G1109-G1115 ◽  
Author(s):  
John R. Grider
Keyword(s):  
Receptor Antagonist ◽  
Physiological Role ◽  
Central Compartment ◽  
Distal Colon ◽  
Rat Colon ◽  
Descending Pathways ◽  
Gastrin Releasing Peptide ◽  
Peristaltic Reflex ◽  
Low Levels

The physiological role of gastrin-releasing peptide (GRP) and of its cognate receptors in regulating the intestinal peristaltic reflex was examined in a three-compartment flat-sheet preparation of rat colon. Mucosal stimulation applied to the central compartment at high, but not low levels of intensity, induced GRP release in the caudad compartment where descending relaxation was measured, but not into the ascending compartment where ascending contraction was measured or into the central compartment where the stimuli were applied. The selective GRP (BB2) receptor antagonist, [d-Phe6,des-Met14]bombesin6–14, inhibited descending relaxation and VIP release in the caudad compartment induced by high but not by low levels of stimulation applied to the mucosa in the central compartment. The selective neuromedin B (BB1) receptor antagonist, BIM-23127, had no effect on descending relaxation or VIP release. Neither the BB1 nor the BB2 antagonist had any effect on ascending contraction or substance P release in the orad compartment. Consistent with the effects of the antagonists on the peristaltic reflex, the BB2 antagonist but not the BB1 antagonist decreased the velocity of propulsion of artificial fecal pellets through isolated segments of guinea pig distal colon. The results indicate that GRP is selectively released from myenteric neurons in descending pathways during the peristaltic reflex and that it acts via BB2 receptors to augment the descending phase of the peristaltic reflex and propulsion.

scholarly journals A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats

1998 ◽  
Vol 274 (5) ◽  
pp. R1500-R1504 ◽  
Author(s):  
A. Ishihara ◽  
T. Tanaka ◽  
A. Kanatani ◽  
T. Fukami ◽  
M. Ihara ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Feeding Behavior ◽  
Physiological Role ◽  
Abnormal Behavior ◽  
Zucker Rats ◽  
Intracerebroventricular Administration ◽  
Feeding Suppression ◽  
Npy Antagonist

Neuropeptide Y (NPY) is one of the most potent orexigenic substances known. 1229U91 was found to be a potent and selective NPY antagonist. To elucidate a physiological role of NPY in hyperphagia in obese animals, we studied the effect of 1229U91 on spontaneous food intake in obese and lean Zucker rats. The food intake of Zucker rats was suppressed by intracerebroventricular administration of 1229U91 more potently in obese than in lean animals without abnormal behavior (31.7 and 67.3% inhibition at doses of 10 and 30 μg, respectively, in Zucker fatty rats and 22.2% inhibition at 30 μg in lean rats). This compound markedly suppressed NPY-induced food intake at 30 μg but did not affect galanin-induced food intake, suggesting that the feeding suppression seen in Zucker fatty and lean rats is pharmacologically and behaviorally specific. These results suggest that NPY is involved in feeding behavior in Zucker fatty rats and that NPY contributes to feeding to a greater degree in Zucker fatty than in lean rats. The hyperphagia in Zucker fatty rats may be due to the abnormal overactivation of the NPYergic system.

The role of photoperiod on the expression of hypothalamic genes regulating appetite in Chevrier’s field mouse (Apodemus chevrieri)

2015 ◽  
Vol 65 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Lin Zhang ◽  
Fang Yang ◽  
Jinhong Cai ◽  
Chunmei Huang ◽  
Zhengkun Wang ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Mrna Expression ◽  
Physiological Role ◽  
Field Mouse ◽  
Related Protein ◽  
Serum Leptin ◽  
Significant Difference ◽  
Agouti Related Protein

The hypothalamus and leptin play a key role in the regulation of food intake. The present study investigated the effects of 4 weeks of short- or long-photoperiod on serum leptin levels and food intake in relation to mRNA expression levels of neuropeptide Y, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript in the hypothalamus of Chevrier’s field mouse (Apodemus chevrieri). There was a significant difference in body fat mass, food intake and neuropeptide Y mRNA expression between the two groups, but serum leptin level, agouti-related protein, pro-opiomelanocortin, and cocaine- and amphetamine-regulated transcript mRNA expression in the hypothalamus were not difference between the two groups. The elevation of neuropeptide Y mRNA regulated neuropeptides in the hypothalamus suggests a physiological role of neuroendocrine factors in food intake during the different photoperiod. We conclude that leptin may be involved in energy balance and body mass regulation.

Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserod

2006 ◽  
Vol 290 (2) ◽  
pp. G319-G327 ◽  
Author(s):  
John R. Grider
Keyword(s):  
Receptor Agonist ◽  
Colonic Mucosa ◽  
Prolonged Exposure ◽  
Receptor Subtype ◽  
Nerve Terminals ◽  
Receptor Desensitization ◽  
Muscle Stretch ◽  
Peristaltic Reflex ◽  
Cgrp Release ◽  
Rate Of Recovery

The intestinal peristaltic reflex induced by mucosal stimulation is mediated by mucosal release of serotonin (5-HT), which acts on 5-HT4 receptors located on CGRP-containing afferent nerve terminals. Exposure of the colonic mucosa to the 5-HT4 receptor agonist tegaserod in the range of 1 nM to 10 μM elicits a peristaltic reflex and stimulates colonic propulsion. The present study was designed to identify the 5-HT4 receptor subtype mediating the reflex and determine whether functionally effective concentrations of tegaserod desensitize the reflex induced by mucosal stimulation. Exposure of rat colonic mucosa to tegaserod in the range of 5 nM to 5 μM for 5 or 10 min caused rapid time- and concentration-dependent desensitization of the peristaltic reflex induced by mucosal stroking, consistent with the operation of a rapidly desensitizing 5-HT4b receptor subtype. Desensitization was accompanied by a decrease in CGRP release. The rate of recovery of peristaltic response depended on the desensitizing concentration of tegaserod: ascending contraction and descending relaxation recovered within 15 min after 5–50 nM tegaserod, 30 min after 0.5 μM, and 60 min after 5 μM. Neither CGRP release nor the peristaltic reflex induced by muscle stretch was affected by 5-HT4 receptor desensitization, providing further evidence that 5-HT does not mediate the reflex induced by muscle stretch. These results suggest in cases of increased 5-HT availability or prolonged exposure, such as colitis, that it is likely the peristaltic reflex will be blunted.

scholarly journals Reelin restricts dendritic growth of interneurons in the neocortex

Development ◽  
2021 ◽  
Vol 148 (17) ◽  
Author(s):  
Mohammad I. K. Hamad ◽  
Petya Petrova ◽  
Solieman Daoud ◽  
Obada Rabaya ◽  
Abdalrahim Jbara ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Ampa Receptors ◽  
Neuronal Migration ◽  
Neurotransmitter Release ◽  
Dendritic Growth ◽  
Embryonic Brain ◽  
Retzius Cells ◽  
Ca2 Channels ◽  
Interneuron Development

ABSTRACT Reelin is a large secreted glycoprotein that regulates neuronal migration, lamination and establishment of dendritic architecture in the embryonic brain. Reelin expression switches postnatally from Cajal-Retzius cells to interneurons. However, reelin function in interneuron development is still poorly understood. Here, we have investigated the role of reelin in interneuron development in the postnatal neocortex. To preclude early cortical migration defects caused by reelin deficiency, we employed a conditional reelin knockout (RelncKO) mouse to induce postnatal reelin deficiency. Induced reelin deficiency caused dendritic hypertrophy in distal dendritic segments of neuropeptide Y-positive (NPY+) and calretinin-positive (Calr+) interneurons, and in proximal dendritic segments of parvalbumin-positive (Parv+) interneurons. Chronic recombinant Reelin treatment rescued dendritic hypertrophy in Relncko interneurons. Moreover, we provide evidence that RelncKO interneuron hypertrophy is due to presynaptic GABABR dysfunction. Thus, GABABRs in RelncKO interneurons were unable to block N-type (Cav2.2) Ca2+ channels that control neurotransmitter release. Consequently, the excessive Ca2+ influx through AMPA receptors, but not NMDA receptors, caused interneuron dendritic hypertrophy. These findings suggest that reelin acts as a ‘stop-growth-signal’ for postnatal interneuron maturation.

Stress-induced mesenteric vasoconstriction in rats is mediated by neuropeptide Y Y1 receptors

1996 ◽  
Vol 270 (2) ◽  
pp. H796-H800 ◽  
Author(s):  
Z. Zukowska-Grojec ◽  
E. K. Dayao ◽  
E. Karwatowska-Prokopczuk ◽  
G. J. Hauser ◽  
H. N. Doods
Keyword(s):  
Neuropeptide Y ◽  
Vascular Resistance ◽  
Cold Water ◽  
Pressor Response ◽  
Physiological Role ◽  
Y1 Receptor ◽  
Y1 Receptors ◽  
Mesenteric Artery Blood Flow ◽  
Mesenteric Vascular Resistance

The physiological role of neuropeptide Y (NPY), a sympathetic cotransmitter and vasoconstrictor, has not been determined yet. We used a specific nonpeptide antagonist to the NPY Y1 receptor [BIBP-3226; (R)-N2-(diphenacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginineamide] to study the involvement of NPY in stress-induced vasoconstriction in the mesenteric bed. In rats subjected to cold water stress (COLD), plasma NPY immunoreactivity levels increased progressively from 0.15 +/- 0.01 to 0.32 +/- 0.05 pmol/ml and remained elevated during recovery. Administration of BIBP-3226 (3 mg.kg-1.h-1 infusion) tended to decrease the stress-induced pressor response and significantly attenuated the post-COLD elevation of blood pressure. The COLD-induced fall in the superior mesenteric artery blood flow and the increase of up to 300% in the mesenteric vascular resistance were either reduced or eliminated by BIBP-3226. Conversely, the Y1 antagonist had no effect on the COLD-induced tachycardia. This study provides the first evidence of the physiological role of NPY. The peptide is released during stress and increases mesenteric vascular resistance via activation of its Y1 receptors. Specific Y1-receptor antagonists may therefore be of potential benefit in prevention or treatment of stress-induced vasospasm.

scholarly journals The Vascular Conducted Response in Cerebral Blood Flow Regulation

2013 ◽  
Vol 33 (5) ◽  
pp. 649-656 ◽  
Author(s):  
Lars Jørn Jensen ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Mechanical Response ◽  
Physiological Role ◽  
Cellular Mechanisms ◽  
Recent Advances ◽  
Cerebrovascular Function ◽  
Arteriolar Wall ◽  
New Finding

Despite recent advances in our understanding of the molecular and cellular mechanisms behind vascular conducted responses (VCRs) in systemic arterioles, we still know very little about their potential physiological and pathophysiological role in brain penetrating arterioles controlling blood flow to the deeper areas of the brain. The scope of the present review is to present an overview of the conceptual, mechanistic, and physiological role of VCRs in resistance vessels, and to discuss in detail the recent advances in our knowledge of VCRs in brain arterioles controlling cerebral blood flow. We provide a schematic view of the ion channels and intercellular communication pathways necessary for conduction of an electrical and mechanical response in the arteriolar wall, and discuss the local signaling mechanisms and cellular pathway involved in the responses to different local stimuli and in different vascular beds. Physiological modulation of VCRs, which is a rather new finding in this field, is discussed in the light of changes in plasma membrane ion channel conductance as a function of health status or disease. Finally, we discuss the possible role of VCRs in cerebrovascular function and disease as well as suggest future directions for studying VCRs in the cerebral circulation.

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