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PubMed · 6311713

Receptor structure and function: an exploratory approach using the thyrotropin receptor as a vehicle.

Abstract

The purpose of this chapter is not to present the final or even correct model of TSH receptor structure and function. Rather, the current speculative model presented is used to open the door to a more broad view of the receptor problem and controversy as it has evolved today. Questions of how we define a receptor are clearly very much in flux and much more difficult than initially considered when a chemical approach is taken. Numerous binding components will be described and their relevance to the physiologic state will be debated. Some will be clearly erroneous in concept--yet the very debate and data will open new ideas and approaches other than repetitive membrane binding or response measurements. The remainder of this book will explore numerous other aspects of receptor structure, regulation and function. The reader may be disturbed by the complexity and extrapolations of data and the weakness of the models. The reader should, however, remember that the receptor is the key link of the cell to its environment. The complexities of this linkage are evident in our continued concern with knowledge of the mechanisms our bodily senses utilize. The controversy that will exist is evident in the arguments we have today over the agents in our environment which affect us and the mechanisms of these effects. It is hoped that this chapter and book will provide both the desire and some reference to follow and review the data in all receptor fields as they emerge in the next several years.

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BibTeXRIS

L D Kohn, S Shifrin. 1982. Receptor structure and function: an exploratory approach using the thyrotropin receptor as a vehicle.. https://pubmed.ncbi.nlm.nih.gov/6311713/

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Evidence for multiple signaling pathways in single squid olfactory receptor neurons.

At least two different G-protein-mediated transduction cascades, the adenylate cyclase and phospholipase C (PLC) pathway, process chemosensory stimuli for various species. In squid olfactory receptor neurons (ORNs), physiological studies indicate that both pathways may be present; however, confirmation of the transduction molecules at the protein level is absent. Here we provide evidence that the G-proteins involved in both adenylate cyclase and PLC pathways are present in squid ORNs (Lolliguncula brevis). We used immunoblotting to show that Galpha(olf), Galpha(q), and a downstream effector, enzyme PLC140, are present in the squid olfactory epithelium (OE). To localize these proteins to one or more of the five morphological cell types described for squid OE, paraformaldehyde-fixed olfactory organs were cryosectioned (10 microm), double-labeled for Galpha(olf), Galpha(q), or PLC140, and imaged. Analysis of serial sections from entire olfactory organs for epithelial area and patterns of immunofluorescence revealed a region of highest immunoreactivity at the anterior half of the organ. At the cellular level, type 1 cells could not be distinguished morphologically and were not included in the analysis. The three labeling patterns observed in type 2 cells were Galpha(q) alone, PLC140 alone, and colocalization of Galpha(q) and PLC140. Subsets of cell types 3, 4, and 5 showed colocalization of Galpha(olf) with Galpha(q) but not with PLC140. These data suggest that the PLC pathway predominates in type 2 cells; however, coexpression of Galpha(olf) with Galpha(q) in cell types 3, 4, and 5 suggests that both pathways may participate in olfactory transduction in non-type 2 squid ORNs.

Adenylyl Cyclases↗

Chronic but not acute intracerebroventricular administration of amyloid beta-peptide(25-35) decreases somatostatin content, adenylate cyclase activity, somatostatin-induced inhibition of adenylate cyclase activity, and adenylate cyclase I levels in the rat hippocampus.

Although alterations in adenylate cyclase (AC) activity and somatostatin (SRIF) receptor density have been reported in Alzheimer's disease, the effects of amyloid beta-peptide (Abeta) on these parameters in the hippocampus are unknown. Our aim was to investigate whether the peptide fragment Abeta(25-35) can affect the somatostatinergic system in the rat hippocampus. Hence, Abeta(25-35) was injected intracerebroventricularly (i.c.v.) to Wistar rats in a single dose or infused via an osmotic minipump connected to a cannula implanted in the right lateral ventricle during 14 days. The animals were decapitated 7 or 14 days after the single injection and 14 days after chronic infusion of the peptide. Chronic i.c.v. infusion of Abeta(25-35) decreased SRIF-like immunoreactive content without modifying the SRIF receptor density, SRIF receptor expression, or the Gialpha(1), Gialpha(2), and Gialpha(3) protein levels in the hippocampus. This treatment, however, caused a decrease in basal and forskolin-stimulated AC activity as well as in the capacity of SRIF to inhibit AC activity. Furthermore, the protein levels of the neural-specific AC type I were significantly decreased in the hippocampus of the treated rats, whereas an increase in the levels of AC V/VI was found, with no alterations in type VIII AC. A single i.c.v. dose of Abeta(25-35) exerted no effect on SRIF content or SRIF receptors but induced a slight decrease in forskolin-stimulated AC activity and its inhibition by SRIF. Because chronic Abeta(25-35) infusion impairs learning and memory whereas SRIF facilitates these functions, the alterations described here might be physiologically important given the decreased cognitive behavior previously reported in Abeta-treated rats.

Adenylyl Cyclases↗

Beta-adrenoceptor blocker treatment and the cardiac beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure.

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Adenylyl Cyclases↗