Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioid receptors (mu, delta and kappa) are known to regulate diverse physiological functions and yet, at the molecular level, they are coupled to a seemingly identical set of G proteins. A recent study has discerned subtle differences between the opioid receptors in their ability to activate the pertussis toxin-insensitive G16. Differences in microarchitecture might be magnified when these receptors are provided with 'non-native' partners. Here, we examined whether the opioid receptors can interact productively with a set of chimeric Galphaq subunits which are known to link many Gi-coupled receptors to phosphoinositide-specific phospholipase C (PI-PLC). The qi5, qo5 and qz5 chimeras have the last five residues of Galphaq replaced by those of Galphai, Galphao and Galphaz, respectively. Except for mu-receptor and qo5, each pair of opioid receptor and Galphaq chimera allowed opioid agonists to stimulate PI-PLC in transfected COS-7 cells. The Galphaq chimera-mediated responses were ligand selective, agonist dose dependent and saturable. The most robust responses were obtained with kappa-receptor and qi5 or qz5, whereas the coupling of delta- and mu-receptors to Galphaq chimeras produced much weaker responses. Among the Galphaq chimeras, qo5 was less efficiently coupled to the opioid receptors. As revealed by radioligand binding assays and immunoblot analysis, differences in the efficiency of coupling were not due to variations in the expression of receptors and Galphaq chimeras. Differences in the magnitude of PI-PLC responses are thus likely to represent structural incompatibility between opioid receptors and Galphaq chimeras, suggesting that each opioid receptor possesses unique structural surfaces for the binding of G proteins.
 ...
PMID:Stimulation of phospholipase C by the cloned mu, delta and kappa opioid receptors via chimeric G alpha(q) mutants. 1005 38

1. Three pharmacological types of opioid receptors, mu, delta and kappa, and their corresponding genes have been identified. Although other types of opioid receptors have been suggested, their existence has not been established unequivocally. A fourth opioid receptor, ORL1, which is genetically closely related to the others, has also been isolated. ORL1 responds to the endogenous agonist nociceptin (orphanin FQ) and displays a pharmacological profile that differs greatly from mu, delta and kappa receptors. 2. All opioid receptors mediate many of their cellular effects via activation of heterotrimeric G-proteins. The mu, delta and kappa receptors are all capable of interacting with the pertussis toxin-sensitive G-protein alpha-subunits Gi1, Gi2, Gi3, Go1, Go2 and the pertussis toxin-insensitive Gz and G16. None of the opioid receptors interacts substantially with Gs and mu receptors do not activate Gq, G11, G12, G13, or G14. 3. Differential coupling of different opioid receptors to most types of G-proteins is marginal. The mu, delta and kappa receptors appear to preferentially activate Go and Gi2 over other pertussis toxin-sensitive G-proteins, although there is evidence that mu receptors show some preference for Gi3. delta Receptors couple more efficiently to G16 than do mu or kappa receptors. 4. There is some evidence that opioid receptors, particularly mu and ORL1 receptors, can also couple to cellular effectors in a G-protein-independent manner. 5. In general, the consequences of activation of any of the opioid receptors in a given cell type depend more on the profile (stoichiometry) of the G-proteins and effectors expressed than on the type of opioid receptor present in the cell. Notions that different types of opioid receptors intrinsically couple preferentially to one type of effector rather than another should, therefore, be discarded.
 ...
PMID:Opioid receptor signalling mechanisms. 1040 72

The family of melatonin receptors is composed of the mt1, MT2, and Mel1c subtypes. The Mel1c is further divided into one long and two short isoforms. A recent study has shown that, unlike mt1 and MT2, the long form of Mel1c is incapable of activating the pertussis toxin-insensitive G16. Here we used three well-characterized Galphaq chimeras to explore the coupling specificity of the melatonin receptors. The qi5, qo5, and qz5 chimeras can link numerous Gi-coupled receptors to the stimulation of phosphoinositide-specific phospholipase C. Both mt1 and MT2 receptors interacted productively with the Galphaq chimeras, while the long form of Mel1c was totally ineffective. Among the Galphaq chimeras, qo5 was less efficiently coupled to the melatonin receptors. Such differential coupling is best explained by structural differences between the melatonin receptors as well as among the Galphaq chimeras. Since the long form of Mel1c receptor possesses an exceptionally large C-terminal tail, we tested the ability of four melatonin receptor C-terminal tail chimeras (Chi 1-4) to interact with the Galphaq chimeras. The presence of the large C-terminal tail of Mel1c in Chi 1 and Chi 3 markedly hindered their coupling to the Galphaq chimeras. On the other hand, the attachment of either the mtl or MT2 C-terminal tail to a Mel1c backbone produced chimeras (Chi 2 and Chi 4) that were capable of activating the Galphaq chimeras. These findings suggest the involvement of C-terminal regions of melatonin receptors in the recognition of G proteins.
 ...
PMID:Chimeric Galphaq subunits can distinguish the long form of the Xenopus Mel1c melatonin receptor from the mammalian mt1 and MT2 melatonin receptors. 1131 28

Melatonin is a pineal hormone involved in neuroendocrine processes in mammals. It has been shown that melatonin inhibits the enzymatic activities of adenylyl cyclases and the transcriptional activities of CREB. In this report, we demonstrate that 2-iodomelatonin (2IMT) treatment on COS-7 cells transfected with melatonin receptors (mt1 and MT2) induces c-Jun N-terminal kinase (JNK) activation, which is pertussis toxin (PTX)-sensitive, Ras/Rac-dependent and may involve Src-family protein tyrosine kinases. Moreover, PTX-insensitive Gs, Gz and G16 are capable of linking activated melatonin receptors to the stimulation of JNK. Agonist stimulation on PTX-pretreated COS-7 cells overexpressing mt1 receptor, Galpha(s) and adenylyl cyclase VI led to increased cAMP accumulation. Stimulation of endogenous mt1 receptors in MCF-7 cells was associated with the activation of both JNK and extracellular signal-regulated kinase (ERK). This report demonstrates the stimulatory effect of melatonin receptors on JNK, and provides experimental evidence for a functional coupling between the G(i)-coupled melatonin receptor and Gs, in terms of adenylyl cyclase activation.
 ...
PMID:Melatonin mt1 and MT2 receptors stimulate c-Jun N-terminal kinase via pertussis toxin-sensitive and -insensitive G proteins. 1181 53

Nucleotides are important extracellular signaling molecules. It has been established that nucleotides are released from damaged cells, activated platelets and endothelial cells. Thus, at the site of vascular injury, the concentrations of extracellular nucleotides can become elevated. Nucleotides have been shown to cause mobilization of intracellular calcium, upregulation of Mac-1 (CD11b/CD18), degranulation, and chemotaxis in human neutrophils. The goal of this work is to investigate the functional characteristics of nucleotide-receptors in human neutrophils. Nucleotides (ATP and UTP), caused intracellular calcium mobilization in a dose dependent manner. Pharmacological characterization using selective agonists (ATP, UTP), pertussis toxin in human neutrophils and human astrocytoma cells 1321N1 stably expressing P2Y2 or P2Y4 receptors, revealed that human neutrophils express only functional P2Y2 receptors. Treatment of neutrophils with pertussis toxin causes a partial inhibition of nucleotide-induced calcium mobilization. Similarly, by using 1321N astrocytoma cells expressing the P2Y2 receptor we confirmed that calcium mobilization is only partially inhibited by pertussis toxin. The partial resistance of P2Y2-mediated intracellular calcium mobilization suggests that this receptor subtype is coupled not only to a Gi protein, but also to a protein belonging to the Gq-family (most likely G16). In conclusion, we have shown that human neutrophils express functional P2Y2 receptors and all the nucleotide responses are mediated by P2Y2 receptor subtype and that P2Y2 receptors are the functional able to trigger intracellular signaling event in human neutrophils through dual activation of different G proteins.
 ...
PMID:[Functional characteristics of nucleotide-receptors in human neutrophils]. 1660 54


<< Previous 1 2