Regulatory peptides
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Regulatory peptides · Jan 2014
Orexin A and B in vitro modify orexins receptors expression and gonadotropins secretion of anterior pituitary cells of proestrous rats.
Orexin A and orexin B (hypocretins) are neuropeptides synthesized mainly by neurons located in the lateral hypothalamus and projections throughout the brain. They are agonists at both the orexin 1 and orexin 2G protein-coupled receptors. They have been related to arousal, sleep and feeding, autonomic and neuroendocrine functions. Their role in the brain control of gonadotropins secretion was postulated in rodents and humans. Previously, we demonstrated the participation of the orexinergic system in attaining successful reproduction in in vivo studies. ⋯ In an in vitro model, we demonstrated a direct effect of orexins on gonadotropins release and orexins receptors expression, underlining the hypothesis that orexins participate in the brain control of pituitary functions.
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Regulatory peptides · Sep 2013
Keratinocytes express cytokines and nerve growth factor in response to neuropeptide activation of the ERK1/2 and JNK MAPK transcription pathways.
Sensory neurons innervating the skin can release neuropeptides that are believed to modulate cellular proliferation, wound healing, pigmentation, and keratinocyte innate immune responses. While the ability of neuropeptides to stimulate keratinocyte production of inflammatory mediators has been demonstrated, there is no information concerning the mechanisms by which neuropeptide activation of keratinocyte cell surface receptors ultimately leads to the up-regulation of mediator production. In this study we used a keratinocyte cell line to identify the presence of substance P (SP) and calcitonin gene-related peptide (CGRP) receptors on keratinocytes and examined the effects of SP and CGRP stimulation on keratinocyte neuropeptide signaling, cell proliferation, and interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and nerve growth factor (NGF) expression. ⋯ Neuropeptide stimulated inflammatory mediatory production in keratinocytes was reversed by ERK1/2 and JNK inhibitors. The current study is the first to observe; 1) that CGRP stimulates keratinocyte expression of CGRP and its receptor complex, 2) that SP and CGRP stimulate IL-6 and TNF-α secretion in keratinocytes, 3) that SP activated all three MAPK families and the NFκB transcriptional signaling pathway in keratinocytes, and 4) that SP and CGRP stimulated inflammatory mediator production in keratinocytes is dependent on ERK1/2 and JNK activation. These studies provide evidence suggesting that disruption of ERK1/2 and JNK signaling may potentially be an effective therapy for inflammatory skin diseases and pain syndromes mediated by exaggerated sensory neuron-keratinocyte signaling.
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Regulatory peptides · Mar 2013
Tolerance to hypophagia induced by prolonged treatment with a CB1 antagonist is related to the reversion of anorexigenic neuropeptide gene expression in the hypothalamus.
It is well established that treatment with rimonabant, a CB1 antagonist, decreases food intake and body weight gain. In part, these responses are mediated by increased activity of hypothalamic neurons related with energy homeostasis. However, food consumption is reversed to basal level during prolonged CB1 antagonist treatment, suggesting tolerance to its anorexigenic effect. ⋯ There was an increase in CB1 mRNA expression in the PVN of rats that received both acute and prolonged-rimonabant treatment. Interestingly, rats subjected to prolonged rimonabant treatment had no changes in food intake, body weight gain, hypothalamic mRNA expression, Fos expression and CRF and CART neuron activation. These data indicate that tolerance to hypophagic effects of CB1 antagonist, rimonabant, is associated with reversion of hypothalamic neuropeptide gene expression related to regulation of energy homeostasis.
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Regulatory peptides · Nov 2012
An inhibitor of leukotriene synthesis affects vasopressin secretion following osmotic stimulus in rats.
Previous studies revealed the presence of LTC(4) synthase in paraventricular vasopressinergic neurons, suggesting a role for leukotrienes (LTs) in certain neuroendocrine system functions. Our aim was to study the effect of an inhibitor of LT synthesis in the release of arginine vasopressin (AVP) following an osmotic stimulus in rats. Male Wistar rats received an intra-cerebroventricular injection of 2 μl of the LT synthesis inhibitor MK-886 (1, 2, or 4 μg/kg), or vehicle (DMSO 5%), 1h before an intraperitoneal injection of hypertonic saline (NaCl 2M) or isotonic saline (NaCl 0.01 M) in a volume corresponding to 1% of body weight. ⋯ As expected, the injection of hypertonic saline significantly increased (P<0.05) the hematocrit, plasma osmolality and plasma AVP levels. While inhibiting LT synthesis by central administration of MK-886 did not cause any additional increase in hematocrit or osmolality, plasma AVP levels were augmented (P<0.05). We conclude that central leukotrienes may have a modulatory role in AVP secretion following an osmotic stimulus, this deserving future studies.
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Regulatory peptides · Nov 2012
Arterial stiffness and novel biomarkers in patients with abdominal aortic aneurysms.
Pulse wave velocity (PWV) constitutes a valid index of arterial stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established vascular calcification inhibitors, highly correlated with inflammation, and cardiovascular events incidence. We investigated the association of PWV with the aforementioned novel biomarkers in patients with abdominal aortic aneurysm (AAA). ⋯ Arterial stiffness, circulating vascular calcification inhibitors and inflammatory mediators seem to be significantly upregulated in patients with AAA. An independent association of PWV with mean blood pressure, OPG and AAA diameter is of clinical importance which requires further investigation.