8 results on '"De Felipe, C."'
Search Results
2. Chemoreceptor activity is normal in mice lacking the NK1 receptor.
- Author
-
Rigual R, Rico AJ, Prieto-Lloret J, de Felipe C, González C, and Donnelly DF
- Subjects
- Animals, Carotid Body cytology, Catecholamines metabolism, Dopamine metabolism, Female, Hypoxia metabolism, Hypoxia physiopathology, Mice, Mice, Knockout, Neurons, Afferent cytology, Norepinephrine metabolism, Receptors, Neurokinin-1 genetics, Sensory Receptor Cells cytology, Signal Transduction physiology, Superior Cervical Ganglion cytology, Superior Cervical Ganglion metabolism, Synaptic Transmission physiology, Visceral Afferents cytology, Carotid Body metabolism, Neurons, Afferent metabolism, Receptors, Neurokinin-1 deficiency, Sensory Receptor Cells metabolism, Substance P metabolism, Visceral Afferents metabolism
- Abstract
Substance P has been proposed to be an important neurotransmitter in the carotid body with the neurokinin 1 (NK1) receptor, mediating excitation between the glomus cells and afferent nerve endings. In order to better understand the role of substance P, this study examined chemoreceptor afferent activity, in vitro, and tissue catecholamine levels and release in adult, wild-type mice and mice lacking the gene for the NK1 receptor (NK1-KO). Groups did not differ significantly in body weight, carotid body dopamine content or carotid body norepinephrine content. In wild-type mice, single unit activity increased from 0.59 +/- 0.14 Hz to 19.78 +/- 2.27 Hz during superfusion with strong hypoxia (PO2 approximately 25 Torr). Chemoreceptor activity in NK1-KO mice, increased from 0.71 +/- 0.23 to 21.50 +/- 3.62 Hz, and neither baseline or peak frequencies were significantly different from the wild-type group. Less severe hypoxia (PO2 approximately 45 torr), evoked peak activities of 12.50 +/- 1.88 and 10.64 +/- 3.72 Hz in wild-type and NK1-KO mice, which were also not significantly different. In response to severe hypoxia, free-tissue catecholamine increased to 4.92 +/- 0.85 microm in wild-type mice and 4.26 +/- 0.63 microm in NK1-KO mice, which were also not significantly different. It may therefore be concluded that loss of NK1 receptors has little effect on chemoreceptor function in the mouse, and thus they play, at best, a minor role in the hypoxic chemoreception process.
- Published
- 2002
- Full Text
- View/download PDF
3. The murine neurokinin NK1 receptor gene contributes to the adult hypoxic facilitation of ventilation.
- Author
-
Ptak K, Burnet H, Blanchi B, Sieweke M, De Felipe C, Hunt SP, Monteau R, and Hilaire G
- Subjects
- Action Potentials drug effects, Action Potentials genetics, Animals, Animals, Newborn, Cell Differentiation drug effects, Female, Gene Expression Regulation, Developmental drug effects, Gene Expression Regulation, Developmental physiology, Hypoxia, Brain genetics, Hypoxia, Brain metabolism, Immunohistochemistry, Male, Medulla Oblongata cytology, Medulla Oblongata metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Net cytology, Nerve Net metabolism, Phrenic Nerve physiology, Receptors, Neurokinin-1 genetics, Respiratory Center cytology, Respiratory Center metabolism, Substance P pharmacology, Synaptic Transmission drug effects, Synaptic Transmission genetics, Cell Differentiation genetics, Medulla Oblongata growth & development, Nerve Net growth & development, Receptors, Neurokinin-1 deficiency, Respiratory Center growth & development, Respiratory Physiological Phenomena drug effects, Substance P metabolism
- Abstract
Substance P and neurokinin-1 receptors (NK1) modulate the respiratory activity and are expressed early during development. We tested the hypothesis that NK1 receptors are involved in prenatal development of the respiratory network by comparing the resting respiratory activity and the respiratory response to hypoxia of control mice and mutant mice lacking the NK1 receptor (NK1-/-). In vitro and in vivo experiments were conducted on neonatal, young and adult mice from wild-type and NK1-/- strains. In the wild strain, immunohistological, pharmacological and electrophysiological studies showed that NK1 receptors were expressed within medullary respiratory areas prior to birth and that their activation at birth modulated central respiratory activity and the membrane properties of phrenic motoneurons. Both the membrane properties of phrenic motoneurons and the respiratory activity generated in vitro by brainstem-spinal cord preparation from NK1-/- neonate mice were similar to that from the wild strain. In addition, in vivo ventilation recordings by plethysmography did not reveal interstrain differences in resting breathing parameters. The facilitation of ventilation by short-lasting hypoxia was similar in wild and NK1-/- neonates but was significantly weaker in adult NK1-/- mice. Results demonstrate that NK1 receptors do appear to be necessary for a normal respiratory response to short-lasting hypoxia in the adult. However, NK1 receptors are not obligatory for the prenatal development of the respiratory network, for the production of the rhythm, or for the regulation of breathing by short-lasting hypoxia in neonates.
- Published
- 2002
- Full Text
- View/download PDF
4. Deficits in visceral pain and hyperalgesia of mice with a disruption of the tachykinin NK1 receptor gene.
- Author
-
Laird JM, Olivar T, Roza C, De Felipe C, Hunt SP, and Cervero F
- Subjects
- Acetic Acid pharmacology, Animals, Behavior, Animal drug effects, Behavior, Animal physiology, Capsaicin pharmacology, Colon drug effects, Colon innervation, Colon physiopathology, Cyclophosphamide pharmacology, Cystitis chemically induced, Cystitis pathology, Cystitis physiopathology, Female, Hyperalgesia chemically induced, Inflammation chemically induced, Inflammation pathology, Inflammation physiopathology, Male, Mice, Mice, Knockout, Mustard Plant, Nociceptors drug effects, Nociceptors pathology, Pain chemically induced, Physical Stimulation, Plant Extracts pharmacology, Plant Oils, Receptors, Neurokinin-1 metabolism, Urinary Bladder drug effects, Urinary Bladder innervation, Urinary Bladder physiopathology, Visceral Afferents drug effects, Visceral Afferents pathology, Hyperalgesia physiopathology, Nociceptors physiopathology, Pain physiopathology, Receptors, Neurokinin-1 genetics, Substance P metabolism, Visceral Afferents physiopathology
- Abstract
Studies in mice lacking genes encoding for substance P or its receptor (NK1), or with NK1 antagonists, have shown that this system contributes to nociception, but the data are complex. Here, we have further examined the role of NK1 receptors in pain and hyperalgesia by comparing nociceptive responses to mechanical and chemical stimulation of viscera and the resulting hyperalgesia and inflammation in NK1 knockout (-/-) and wild-type (+/+) mice. We concentrated on visceral nociception because substance P is expressed by a much greater proportion of visceral than cutaneous afferents. NK1 -/- mice showed normal responses to visceral mechanical stimuli, measured as behavioural responses to intraperitoneal acetylcholine or hypertonic saline or reflex responses to colon distension in anaesthetized mice, although -/- mice failed to encode the intensity of noxious colon distensions. In contrast, NK1 -/- mice showed profound deficits in spontaneous behavioural reactions to an acute visceral chemical stimulus (intracolonic capsaicin) and failed to develop referred hyperalgesia or tissue oedema. However, in an identical procedure, intracolonic mustard oil evoked normal spontaneous behaviour, referred hyperalgesia and oedema in -/- mice. The inflammatory effects of capsaicin were abolished by denervation of the extrinsic innervation of the colon in rats, whereas those of mustard oil were unchanged, showing that intracolonic capsaicin evokes neurogenic inflammation, but mustard oil does not. Tests of other neurogenic inflammatory stimuli in NK1 -/- mice revealed impaired behavioural responses to cyclophosphamide cystitis and no acute reflex responses or primary hyperalgesia to intracolonic acetic acid. We conclude that NK1 receptors have an essential role mediating central nociceptive and peripheral inflammatory responses to noxious stimuli that evoke neurogenic inflammation, and modulating responses to noxious mechanical stimuli. We propose that two separate hyperalgesia pathways exist, one of which is NK1 receptor dependent, whereas the other does not require intact substance P/NK1 signalling.
- Published
- 2000
- Full Text
- View/download PDF
5. Endogenously produced substance P contributes to lymphocyte proliferation induced by dendritic cells and direct TCR ligation.
- Author
-
Lambrecht BN, Germonpré PR, Everaert EG, Carro-Muino I, De Veerman M, de Felipe C, Hunt SP, Thielemans K, Joos GF, and Pauwels RA
- Subjects
- Animals, Antigen Presentation, Cell Division immunology, Dendritic Cells cytology, Ligands, Lymphocyte Activation immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Signal Transduction immunology, T-Lymphocytes cytology, Cell Communication immunology, Dendritic Cells immunology, Receptors, Antigen, T-Cell immunology, Substance P immunology, T-Lymphocytes immunology
- Abstract
Substance P (SP) is an immunoregulatory tachykinin which augments antigen- and mitogen-induced lymphocyte proliferation via signaling through the neurokinin-1 receptor (NK1-R). Non-neuronal cells of the immune system such as monocytes, T lymphocytes and eosinophils can be a source of SP. We have investigated if antigen-presenting dendritic cells (DC) produce SP. DC were grown from bone marrow precursors using a cocktail of GM-CSF, IL-4 and Flt-3 ligand. Reverse transcriptase-PCR amplification using primers for the mouse preprotachykinin-A gene and direct DNA sequencing of amplified products from purified DC demonstrated the presence of the gamma-transcript of the gene, coding for SP and neurokinin A. At the protein level, mouse DC expressed SP as determined by an enzyme immunoassay and confirmed by immunostaining. The functional role of endogenous SP release was determined. During the interaction with syngeneic or allogeneic DC, the addition of a specific NK1-R antagonist partly reduced proliferation in responding T lymphocytes. This was confirmed by using responders derived from NK1-R-deficient mice. In the absence of DC, proliferation of T cells induced by direct TCR ligation and soluble CD28 was partly dependent on signaling through NK1-R, revealing an autocrine effect of SP production by T cells. In conclusion, these results demonstrate that endogenously produced SP contributes to T cell proliferation induced by DC or TCR / CD28 stimulation.
- Published
- 1999
- Full Text
- View/download PDF
6. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P.
- Author
-
De Felipe C, Herrero JF, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, Laird JM, Belmonte C, Cervero F, and Hunt SP
- Subjects
- Analgesics, Opioid pharmacology, Animals, Electric Stimulation, Electromyography, Female, Formaldehyde pharmacology, Gene Targeting, Hyperalgesia etiology, Male, Mice, Mice, Inbred C57BL, Morphine pharmacology, Mutagenesis, Neuritis chemically induced, Neuritis physiopathology, Pain Threshold, Physical Stimulation, Receptors, Neurokinin-1 deficiency, Receptors, Neurokinin-1 genetics, Stress, Physiological physiopathology, Aggression, Analgesia, Pain, Receptors, Neurokinin-1 physiology, Substance P physiology
- Abstract
The peptide neurotransmitter substance P modulates sensitivity to pain by activating the neurokinin-1 (NK-1) receptor, which is expressed by discrete populations of neurons throughout the central nervous system. Substance P is synthesized by small-diameter sensory 'pain' fibres, and release of the peptide into the dorsal horn of the spinal cord following intense peripheral stimulation promotes central hyperexcitability and increased sensitivity to pain. However, despite the availability of specific NK-1 antagonists, the function of substance P in the perception of pain remains unclear. Here we investigate the effect of disrupting the gene encoding the NK-1 receptor in mice. We found that the mutant mice were healthy and fertile, but the characteristic amplification ('wind up') and intensity coding of nociceptive reflexes was absent. Although substance P did not mediate the signalling of acute pain or hyperalgesia, it was essential for the full development of stress-induced analgesia and for an aggressive response to territorial challenge, demonstrating that the peptide plays an unexpected role in the adaptive response to stress.
- Published
- 1998
- Full Text
- View/download PDF
7. Modulation of chemotropism in the developing spinal cord by substance P.
- Author
-
De Felipe C, Pinnock RD, and Hunt SP
- Subjects
- Animals, Animals, Newborn, Axons physiology, Axons ultrastructure, Calcium metabolism, Central Nervous System chemistry, Central Nervous System cytology, Central Nervous System metabolism, Culture Techniques, Neurons chemistry, Neurons ultrastructure, Rats, Receptors, Neurokinin-1 analysis, Receptors, Neurokinin-1 metabolism, Spinal Cord cytology, Substance P analysis, Substance P pharmacology, Central Nervous System embryology, Chemotactic Factors metabolism, Neurons physiology, Spinal Cord embryology, Substance P metabolism
- Abstract
Developing axons find their targets through direct contact with cues in the extracellular environment and in response to gradients of diffusible factors. The floor plate, a neuroepithelial structure, guides developing commissural axons in the spinal cord by release of chemoattractants. Floor plate cells express neurokinin-1 receptors, and a transiently appearing subpopulation of commissural axons contains substance P, the neuropeptide ligand for this receptor. Substance P increases the amount of axon outgrowth from dorsal horn explants cocultured with floor plate explants. Results of experiments with embryonic rats suggest that substance P released from pioneering neuronal pathways may regulate the release of chemoattractants from floor plate cells.
- Published
- 1995
- Full Text
- View/download PDF
8. The use of NK-1 receptor null mice to assess the significance of substance P in the carotid body function
- Author
-
Alberto José Rico Martín, Prieto-Lloret J, Df, Donnelly, De Felipe C, Gonzalez C, and Rigual R
- Subjects
Mice, Knockout ,Carotid Body ,Mice ,Carotid Sinus ,Animals ,Female ,In Vitro Techniques ,Receptors, Neurokinin-1 ,Substance P ,Hypoxia ,Immunohistochemistry ,Chemoreceptor Cells
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.