Modulation by brain natriuretic peptide of GABA receptors on rat retinal ON-type bipolar cells.
Natriuretic peptides (NPs) may work as neuromodulators through their associated receptors [NP receptors (NPRs)]. By immunocytochemistry, we showed that NPR-A and NPR-B were expressed abundantly on both ON-type and OFF-type bipolar cells (BCs) in rat retina, including the dendrites, somata, and axon terminals. Whole-cell recordings made from isolated ON-type BCs further showed that brain natriuretic peptide (BNP) suppressed GABAA receptor-, but not GABAC receptor-, mediated currents of the BCs, which was blocked by the NPR-A antagonist anantin. The NPR-C agonist c-ANF [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANF(4-23)-NH2] did not suppress GABAA currents. The BNP effect on GABAA currents was abolished with preincubation with the pGC-A/B antagonist HS-142-1 but mimicked by application of 8-bromoguanosine-3',5'-cyclomonophosphate. These results suggest that elevated levels of intracellular cGMP caused by activation of NPR-A may mediate the BNP effect. Internal infusion of the cGMP-dependent protein kinase G (PKG) inhibitor KT5823 essentially blocked the BNP-induced reduction of GABAA currents. Moreover, calcium imaging showed that BNP caused a significant elevation of intracellular calcium that could be caused by increased calcium release from intracellular stores by PKG. The BNP effect was blocked by the ryanodine receptor modulators caffeine, ryanodine, and ruthenium red but not by the IP3 receptor antagonists heparin and xestospongin-C. Furthermore, the BNP effect was abolished after application of the blocker of endoplasmic reticulum Ca2+-ATPase thapsigargin and greatly reduced by the calmodulin inhibitors W-7 and calmidazolium. We therefore conclude that the increased calcium release from ryanodine-sensitive calcium stores by BNP may be responsible for the BNP-caused GABAA response suppression in ON-type BCs through stimulating calmodulin.
Yu
Yong-Chun
YC
Institute of Neurobiology, Fudan University, Shanghai 200433, China.
Cao
Li-Hui
LH
Yang
Xiong-Li
XL
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D058787:GABA-A Receptor Antagonists; D006162:Guanylate Cyclase / Q000187:drug effects* / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D020097:Natriuretic Peptide, Brain / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D010080:Oxazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D018079:Receptors, GABA / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects*; D051245:Retinal Bipolar Cells / Q000187:drug effects* / Q000502:physiology; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D000099242:Atrial Natriuretic Factor Receptor B
D009320:Atrial Natriuretic Factor; D002110:Caffeine; D002118:Calcium; D015220:Calcium Channels; D000252:Calcium-Transporting ATPases; D002147:Calmodulin; D002227:Carbazoles; D006152:Cyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D058787:GABA-A Receptor Antagonists; D006162:Guanylate Cyclase; D006493:Heparin; D007093:Imidazoles; D007211:Indoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D020097:Natriuretic Peptide, Brain; D010080:Oxazoles; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011134:Polysaccharides; D047428:Protein Kinase Inhibitors; D017461:Receptors, Atrial Natriuretic Factor; D018160:Receptors, Cytoplasmic and Nuclear; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D012430:Ruthenium Red; D012433:Ryanodine; D019837:Ryanodine Receptor Calcium Release Channel; D019284:Thapsigargin; D005680:gamma-Aminobutyric Acid; D000099242:Atrial Natriuretic Factor Receptor B; C087200:GABA-C receptor; C072551:HS 142-1; C495963:natriuretic peptide precursor type B, rat; C108644:xestospongin A; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; C073601:KT 5823; C068090:anantin; C016276:8-bromocyclic GMP; C031938:calmidazolium; C091715:atrial natriuretic factor receptor A