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1.
目的 观察养血柔肝中药归参止痒方对血虚肝旺型老年皮肤瘙痒症患者临床疗效及其对干细胞因子(SCF)及强啡肽(DYN)的影响,探讨其治疗老年皮肤瘙痒症的作用机制。 相似文献
2.
Diane M. Burnard Quentin J. Pittman Brian A. MacVicar 《Journal of neuroendocrinology》1991,3(4):433-439
Intracellular recordings were obtained from pituicytes in the neural lobe of the isolated rat pituitary. Like other glia, pituicytes lacked action potentials in response to depolarizing current injection, but they tended to have more positive resting membrane potentials and higher input resistances than astrocytes in other preparations. Dye-coupling typical of astrocytes was also demonstrated amongst pituicytes, and their morphologies were similar to those of pituicytes stained for glial fibrillary acidic protein. Action potentials, anode-break spikes or barium spikes were not observed in pituicytes, even under conditions that maximized the elicitation of Ca2+-dependent responses. This suggests that pituicytes either have no or a very low density of Ca2+ channels or Ca2+ currents that are too small to generate action potentials. Dynorphin A (1–13), a kappa-opioid agonist, produced long-lasting increases in pituicyte input resistance with no significant changes in resting membrane potential. Dynorphin's action was concentration-dependent and was blocked by the opioid antagonist naloxone. This is consistent with previous reports demonstrating kappa-opioid receptors on pituicytes in the neurohypophysis. The β-adrenergic agonist isoproterenol (100 μM) reversed the increases in pituicyte input resistance produced by opioid application, with no significant changes in resting membrane potential. The fact that pituicytes responded to neurotransmitters suggests a functional link between pituicytes and neurosecretory nerve fibres. 相似文献
3.
Co-localization of neuropeptide Y, vasoactive intestinal polypeptide and dynorphin in non-noradrenergic axons of the guinea pig uterine artery 总被引:5,自引:0,他引:5
Two major populations of perivascular axons containing immunoreactivity to neuropeptide Y (NPY) have been revealed in the main uterine artery of the guinea pig by immunohistochemical procedures which allow the simultaneous visualization of two antigens. One population contained immunoreactivity to dopamine-beta-hydroxylase (D beta H) and was presumably noradrenergic. The other main population of axons with NPY-like immunoreactivity (NPY-LI) did not have D beta H-like immunoreactivity (D beta H-LI) and was presumably non-noradrenergic. These non-noradrenergic axons also contained immunoreactivity to vasoactive intestinal polypeptide (VIP) and dynorphin (DYN). Indeed, nearly all axons with VIP-LI also contained NPY-LI and DYN-like immunoreactivity (DYN-LI). NPY constricted the uterine artery perfused in vitro, whilst VIP dilated uterine arteries preconstricted with noradrenaline or NPY. Thus, we have evidence for the coexistence of a vasoconstrictor peptide and a vasodilator peptide in the same non-noradrenergic perivascular axons, which also contain an opioid peptide, dynorphin. 相似文献
4.
Abstract: We previously reported that the novel dynorphin A (Dyn A, Tyr‐Gly‐Gly‐Phe‐Leu‐Arg‐Arg‐Ile‐Arg‐Pro‐Lys‐Leu‐Lys‐Trp‐Asp‐Asn‐Gln) analog arodyn (Ac[Phe1,2,3,Arg4,d ‐Ala8]Dyn A‐(1–11)NH2, Bennett, M.A., Murray, T.F. & Aldrich, J.V. (2002) J. Med. Chem. vol. 45, pp. 5617–5619) is a κ opioid receptor‐selective peptide [Ki(κ) = 10 nm , Ki ratio (κ/μ/δ) = 1/174/583] which exhibits antagonist activity at κ opioid receptors. In this study, a series of arodyn analogs was prepared and evaluated to explore the structure–activity relationships (SAR) of this peptide; this included an alanine scan of the entire arodyn sequence, sequential isomeric d ‐amino acid substitution in the N‐terminal ‘message’ sequence, NMePhe substitution individually in positions 1–3, and modifications in position 1. The results for the Ala‐substituted derivatives indicated that Arg6 and Arg7 are the most important residues for arodyn's nanomolar binding affinity for κ opioid receptors. Ala substitution of the other basic residues (Arg4, Arg9 and Lys11) resulted in lower decreases in affinity for κ opioid receptors (three‐ to fivefold compared with arodyn). Of particular interest, while [Ala10]arodyn exhibits similar κ opioid receptor binding as arodyn, it displays higher κ vs. μ opioid receptor selectivity [Ki ratio (κ/μ) = 1/350] than arodyn because of a twofold loss in affinity at μ opioid receptors. Surprisingly, the Tyr1 analog exhibits a sevenfold decrease in κ opioid receptor affinity, indicating that arodyn displays significantly different SAR than Dyn A; [Tyr1]arodyn also unexpectedly exhibits inverse agonist activity in the adenylyl cyclase assay using Chinese hamster ovary cells stably expressing κ opioid receptors. Substitution of NMePhe in position 1 gave [NMePhe1]arodyn which exhibits high affinity [Ki(κ) = 4.56 nm ] and exceptional selectivity for κ opioid receptors [Ki ratio (κ/μ/δ) = 1/1100/>2170]. This peptide exhibits antagonistic activity in the adenylyl cyclase assay, reversing the agonism of 10 nm Dyn A‐(1–13)NH2. Thus [NMePhe1]arodyn is a highly κ opioid receptor‐selective antagonist that could be a useful pharmacological tool to study κ opioid receptor‐mediated activities. 相似文献
5.
Corey Baimel Selena E Bartlett Lih-Chu Chiou Andrew J Lawrence John W Muschamp Omkar Patkar Li-Wei Tung Stephanie L Borgland 《British journal of pharmacology》2015,172(2):334-348
Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.
LINKED ARTICLES
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 相似文献6.
7.
F C Machado V O Zambelli A C O Fernandes A S Heimann Y Cury G Picolo 《British journal of pharmacology》2014,171(4):961-972
Background and Purpose
Crotalphine is an antinociceptive peptide that, despite its opioid-like activity, does not induce some of the characteristic side effects of opioids, and its amino acid sequence has no homology to any known opioid peptide. Here, we evaluated the involvement of the peripheral cannabinoid system in the crotalphine effect and its interaction with the opioid system.Experimental Approach
Hyperalgesia was evaluated using the rat paw pressure test. Involvement of the cannabinoid system was determined using a selective cannabinoid receptor antagonist. Cannabinoid and opioid receptor activation were evaluated in paw slices by immunofluorescence assays using conformation state-sensitive antibodies. The release of endogenous opioid peptides from skin tissue was measured using a commercial enzyme immunoassay (EIA).Key Results
Both p.o. (0.008–1.0 μg·kg−1) and intraplantar (0.0006 μg per paw) administration of crotalphine induced antinociception in PGE2-induced hyperalgesia. Antinociception by p.o. crotalphine (1 μg·kg−1) was blocked by AM630 (50 μg per paw), a CB2 receptor antagonist, and by antiserum anti-dynorphin A (1 μg per paw). Immunoassay studies confirmed that crotalphine increased the activation of both κ-opioid (51.7%) and CB2 (28.5%) receptors in paw tissue. The local release of dynorphin A from paw skin was confirmed by in vitro EIA and blocked by AM630.Conclusions and Implications
Crotalphine-induced antinociception involves peripheral CB2 cannabinoid receptors and local release of dynorphin A, which is dependent on CB2 receptor activation. These results enhance our understanding of the mechanisms involved in the peripheral effect of crotalphine, as well as the interaction between the opioid and cannabinoid systems. 相似文献8.
9.
The present study was designed to investigate the effect of the kappa opioid receptor (KOR) agonist, dynorphin A (Dyn), on aqueous humor dynamics (intraocular pressure (IOP), aqueous humor flow rate (AFR)), pupil diameter (PD) and atrial natriuretic peptide (ANP) levels in the aqueous humor of the rabbit. Topical and unilateral application of Dyn caused dose-related, bilateral reductions in IOP and AFR. An intermediate dose of Dyn (33 microg) caused bilateral mydriasis whereas a higher dose (100 microg) caused unilateral miosis. The Dyn-induced reduction in IOP and aqueous flow rate as well as the mydriasis were antagonized by nor-binaltorphimine (nor-BNI), a relatively selective KOR antagonist. In addition to the effects on IOP, PD and AFR, Dyn caused dose-related increases in aqueous ANP levels that was attenuated by nor-BNI. The present study indicates that Dyn reduces IOP, in part, by reducing AFR. Moreover, the increase in ANP levels could be involved in the Dyn-induced reductions in IOP and AFR. Based upon the inhibitory effects of nor-BNI, these Dyn-induced events are due, in part, to the activation of KORs in the ciliary processes of the eye. 相似文献
10.
Andree Turcotte Jean-Marc Lalonde Serge St-Pierre Simon Lemaire 《Chemical biology & drug design》1984,23(4):361-367
Dynorphin-(1–13) (Dyn-(1–13)) and its analogs substituted by single introduction of Ala in positions 1–11 were synthesized by the solid-phase method and purified by high pressure liquid chromatography. Relative potencies of the synthetic compounds were determined by their ability to inhibit electrically-evoked contractions of the guinea pig ileum (GPI) and of the mouse vas deferens (MVD) and to compete with [3H]-etorphine for opiate receptors in rat brain homogenates. Introduction of Ala in positions 1 and 4 of Dyn-(1–13) provoked most important decreases in the activity of the molecule in the three assays (relative potency of 0.2% or less). Substitution of Ala in positions 2 or 5, but not 3, also severely decreased the potency of the peptide in the smooth muscle preparations (0.6–5.0% activity). However, the opiate receptor binding assay was less sensitive to the replacement of residue in position 2 (20% activity) than that in positions 3 or 5 (12% and 6% relative potencies, respectively). In the GPI assay and the opiate binding test, the other substitutions which greatly lowered the potency of the molecule were seen in positions 6, 7, 9 and 11, four basic residues. Among these, Arg6 and Arg7 were demonstrated to be the most important in the three biological tests. Finally, the replacement of Ile8 by Ala increased the relative potency of Dyn-(1–13) up to 191% and 900% in the MVD and the opiate binding tests, respectively. 相似文献