Unmasking the functions of the chromaffin cell α ₇ nicotinic receptor by using short pulses of acetylcholine and selective blockers

Abstract

Methyllycaconitine (

Modulatory Mechanism of the Endogenous Peptide Catestatin on Neuronal Nicotinic Acetylcholine Receptors and Exocytosis

“…5B). Nevertheless, because the only concentration of ACh used to build these curves (100 M) matches with the EC 50 values of ACh acting on ␣ 3 ␤ 4 and ␣ 7 nAChRs (98 and 95 M, respectively), and similar IC 50 values for catestatin blockade on both receptor types were found, it is possible to conclude that the two main classes of nAChRs controlling the catecholamine release at the splanchnic-chromaffin cell synapse (López et al, 1998) are potential targets for catestatin. Moreover, the fact that the rest of the nAChR subtypes tested do not differ significantly in their sensitivity to the peptide suggests that catestatin might be a ubiquitous regulator of the cholinergic neurotransmission in other areas in addition to the adrenal medulla, i.e., the brain, where ␣ 4 and ␤ 2 nAChR subunits predominate (Gopalakrishnan et al, 1996), or sympathetic ganglia that express ␣ 3, ␤ 2 , ␣ 7 , and ␤ 4 nAChR subunits (Yu and Role, 1998;Xu et al, 1999) and where endogenously formed catestatin has been documented (Taylor et al, 2000).…”

“…Furthermore, it has been suggested that nAChRs containing ␣ 3 and ␤ 4 subunits are dominant in the control of catecholamine secretion from these cells (Wilson and Kirshner 1977;Kumakura et al, 1980;Trifaró and Lee, 1980;Kilpatrick et al, 1981). However, bovine chromaffin cells additionally express ␣ 7 nAChRs (García-Guzman et al, 1995), which are also functional (López et al, 1998). Therefore, it was of interest to know whether catestatin blocked nAChR subunit combinations other than the ␣ 3 ␤ 4 .…”

“…Figure 5A (left) shows I ACh traces obtained after application of 5 sec pulses of 100 M ACh (applied 2 min apart) onto an oocyte expressing ␣ 7 receptors. The control current relaxed very quickly, likely because of the well established fast desensitization of this receptor subtype after its stimulation with agonists (López et al, 1998;Papke and Thinschmidt, 1998;Herrero et al, 1999). Catestatin (1 M), added 1 min before and during the ACh pulse, blocked the current by 66%.…”

“…Additionally, the previous experiments did not provide information concerning the subtype of nAChR preferentially blocked by catestatin. This is an important issue, because at least two different classes of nAChRs, most likely formed by the combination of ␣ 3 and ␤ 4 subunits or ␣ 7 subunits that bind ␣-bungarotoxin, have been implicated in the control of catecholamine secretion in chromaffin cells (Criado et al, 1992;Campos-Caro et al, 1997;López et al, 1998).…”

Functional Characterization of α9-Containing Cholinergic Nicotinic Receptors in the Rat Adrenal Medulla: Implication in Stress-Induced Functional Plasticity

“…Multiple ␣ and ␤ subunits have been identified in rat chromaffin cells (Di Angelantonio et al, 2003;Sala et al, 2008). Although the ␣3 subunit constitutes a major component of nAChRs activated in response to synaptically released acetylcholine (Criado et al, 1992;Nooney and Feltz, 1995;Barbara and Takeda, 1996), ␣7-built receptors are also involved in acetylcholine-mediated responses (Ló pez et al, 1998;Martin et al, 2003Martin et al, , 2005. The expression of ␣9 and ␣10 subunits in rat chromaffin cells (L. A. Olivos-Oré, L. Solís, C. Montiel, and A. R. Artalejo, unpublished observations) extends the tissular distribution of ␣9/␣10 nAChRs to a neuroendocrine tissue and raises the question of their role.…”