Genetic deletion of somatostatin receptor 1 alters somatostatinergic transmission in the mouse retina.
In the mammalian retina, sparse amacrine cells contain somatostatin-14 (SRIF) which acts at multiple levels of neuronal circuitry through distinct SRIF receptors (sst(1-5)). Among them, the sst1 receptor has been localised to SRIF-containing amacrine cells in the rat and rabbit retina. Little is known about sst1 receptor localisation and function in the mouse retina. We have addressed this question in the retina of mice with deletion of sst1 receptors (sst1 KO mice). In the retina of wild type (WT) mice, sst1 receptors are localised to SRIF-containing amacrine cells, whereas in the retina of sst1 KO mice, sst1 receptors are absent. sst1 receptor loss causes a significant increase in retinal levels of SRIF, whereas it does not affect SRIF messenger RNA indicating that sst1 receptors play a role in limiting retinal SRIF at the post-transcriptional level. As another consequence of sst1 receptor loss, levels of expression of sst2 receptors are significantly higher than in control retinas. Together, these findings provide the first demonstration of prominent compensatory regulation in the mouse retina as a consequence of a distinct SRIF receptor deletion. The fact that in the absence of the sst1 receptor, retinal SRIF increases in concomitance with an increase in sst2 receptors suggests that SRIF may regulate sst2 receptor expression and that this regulatory process is controlled upstream by the sst1 receptor. This finding can be important in the design of drugs affecting SRIF function, not only in the retina, but also elsewhere in the brain.
Dal Monte
Massimo
M
Dipartimento di Fisiologia e Biochimica, Università di Pisa, via San Zeno 31, 56127 Pisa, Italy.
Petrucci
Cristina
C
Vasilaki
Anna
A
Cervia
Davide
D
Grouselle
Dominique
D
Epelbaum
Jacques
J
Kreienkamp
Hans-Jurgen
HJ
Richter
Dietmar
D
Hoyer
Daniel
D
Bagnoli
Paola
P
D000818:Animals; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D012160:Retina / Q000378:metabolism*; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology*
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D013004:Somatostatin