The metabotropic glutamate receptors of the vestibular organs.
This research sought to test the presence and function of metabotropic excitatory amino acid receptors (mGluR) in the frog semicircular canal (SCC). The mGluR agonist +/- 1-aminocyclopentane-trans-1,3-dicarboxylate (ACPD) produced an increase in afferent firing rates of the ampullar nerve of the intact posterior canal. This increase was not due to a stimulation of cholinergic efferent terminals or the acetylcholine (ACh) receptor, since atropine, in concentrations which blocked the response to exogenous acetylcholine, did not affect the response to ACPD. Likewise, ACPD effects were not due to stimulation of postsynaptic NMDA receptors, since the NMDA antagonist D(-)-2-amino-5-phosphonopentanoate (AP-5) did not affect the response to ACPD, reinforcing the reported selectivity of ACPD for mGluRs. When the SCC was superfused with artificial perilymph known to inhibit hair cell transmitter release (i.e. low Ca-high Mg), ACPD failed to increase afferent firing. This suggests that the receptor activated by ACPD is located on the hair cell. Pharmacological evidence suggested that the mGluRs involved in afferent facilitation belong to Group I (i.e. subtypes 1 and 5). In fact, the Group III agonist AP-4 had no effect, and the ACPD facilitatory effect was blocked by the Group I mGluR antagonists (S)-4-carboxyphenylglycine (CPG) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA). Additional pharmacological evidence supported the presence of Group I mGluRs. Interestingly, the mGluR antagonists, AIDA and 4CPG, by themselves did not affect the resting firing rates of ampullar afferents. This may suggest that the mGluRs are not involved in resting activity but perhaps only in evoked activity (as suggested in Guth et al. (1991) Hear. Res. 56, 69-78). In addition, the mRNA for the mGluR1 has been detected in hair cells of both SCC, utricle, and saccule. In summary, the evidence points to an mGluR localized to the hair cell (i.e. an autoreceptor) which may be activated to produce a positive feedback augmentation of evoked but not resting transmitter release and thus affect afferent activity.
Guth
P S
PS
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA. pguth@mailhost.tcs.tulane.edu
Holt
J C
JC
Perin
P
P
Athas
G
G
Garcia
M
M
Puri
A
A
Zucca
G
G
Botta
L
L
Valli
P
P
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005246:Feedback; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008954:Models, Biological; D012313:RNA / Q000235:genetics; D011894:Rana pipiens; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D012665:Semicircular Canals / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014722:Vestibule, Labyrinth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D012313:RNA