scholarly journals Full activation of an α7-α3β4 nicotinic receptor complex avoids receptor desensitization in human chromaffin cells

2020 ◽  
Author(s):  
Amanda Jiménez-Pompa ◽  
Sara Sanz-Lázaro ◽  
José Medina-Polo ◽  
Carmen González-Enguita ◽  
Jesús Blázquez ◽  
...  

Abstractα7 nicotinic receptors have been involved in numerous pathologies. A hallmark of these receptors is their extremely fast desensitization, a process not fully understood yet. Here we show that human native α7 and α3β4 nicotinic receptors physically interact in human chromaffin cells of adrenal glands. The full activation of this α7-α3β4 receptor complex avoids subtypes receptor desensitization, leading to gradual increase of currents with successive acetylcholine pulses. Instead, full and partial activation with choline of α7 and α3β4 subtypes, respectively, of this linked receptor leads to α7 receptor desensitization. Therefore choline, a product of the acetylcholine hydrolysis, acts as a brake by limiting the increase of currents by acetylcholine. Very importantly, the efficiency of the α7-α3β4 interaction diminishes in subjets older than 50 years, accordingly increasing receptor desensitization and decreasing nicotinic currents. These results open a new line of research to achieve improved therapeutic treatments for nicotinic receptors related diseases.

2006 ◽  
Vol 96 (3) ◽  
pp. 1196-1202 ◽  
Author(s):  
Gloria Arroyo ◽  
Jorge Fuentealba ◽  
Natalia Sevane-Fernández ◽  
Marcos Aldea ◽  
Antonio G. García ◽  
...  

This study was designed to examine the kinetics of neurotransmitter release using the carbon fiber amperometric technique on cells in slices of mouse adrenal glands superfused with bicarbonate phosphate buffer–based solutions. The exocytotic amperometric response evoked by electrical stimulation was significantly faster than that produced after exogenous application of ACh or K+. Splanchnic nerve–evoked neurotransmitter release was blocked by hexamethonium, indicating the involvement of ACh nicotinic receptors. We discuss the implications of our data for understanding the mechanisms underlying the vesicle fusion process.


Author(s):  
H.B. Pollard ◽  
C.E. Creutz ◽  
C.J. Pazoles ◽  
J.H. Scott

Exocytosis is a general concept describing secretion of enzymes, hormones and transmitters that are otherwise sequestered in intracellular granules. Chemical evidence for this concept was first gathered from studies on chromaffin cells in perfused adrenal glands, in which it was found that granule contents, including both large protein and small molecules such as adrenaline and ATP, were released together while the granule membrane was retained in the cell. A number of exhaustive reviews of this early work have been published and are summarized in Reference 1. The critical experiments demonstrating the importance of extracellular calcium for exocytosis per se were also first performed in this system (2,3), further indicating the substantial service given by chromaffin cells to those interested in secretory phenomena over the years.


1997 ◽  
Vol 17 (17) ◽  
pp. 6554-6564 ◽  
Author(s):  
Manuel Criado ◽  
Eduardo Domı́nguez del Toro ◽  
Carmen Carrasco-Serrano ◽  
Frazer I. Smillie ◽  
José M. Juı́z ◽  
...  

1982 ◽  
Vol 242 (3) ◽  
pp. E137-E145 ◽  
Author(s):  
M. H. Carvalho ◽  
J. C. Prat ◽  
A. G. Garcia ◽  
S. M. Kirpekar

Ionomycin, a polyether antibiotic, stimulated the secretion of catecholamines and dopamine beta-hydroxylase from perfused adrenal glands and [3H]norepinephrine ([3H]NE) from spleens of the cat. Release was calcium dependent, and strontium or barium did not substitute for calcium. Ionomycin failed to release [3H]NE from reserpinized spleens. High magnesium did not interfere in the ionomycin response, but lanthanum and manganese blocked it. Ionomycin response that was pH dependent was not affected by potassium depolarization. The secretory response to ionomycin was enhanced when both glycolysis and oxidative metabolism were inhibited. It is concluded that ionomycin introduces calcium into the chromaffin cells and adrenergic nerve terminals to cause the secretory response and that a rise in intracellular calcium may be an adequate stimulus for secretion.


FEBS Letters ◽  
1995 ◽  
Vol 362 (1) ◽  
pp. 15-18 ◽  
Author(s):  
Ricardo Granja ◽  
JoséM Fernández-Fernández ◽  
Victor Izaguirre ◽  
Carmen González-García ◽  
Valentin Ceña

1992 ◽  
Vol 573 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Janet M. Nooney ◽  
Jeremy J. Lambert ◽  
Vincent A. Chiappinelli

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