Actions of 8-bromo-cyclic-GMP on neurones in the rat thalamus in vivo and in vitro.
The diffusible intercellular messenger nitric oxide may have a modulatory role in the thalamus and this action may be mediated via activation of soluble guanylate cyclase. In order to investigate this possibility, we applied the cyclic-GMP analogue 8-Bromo-cyclic-GMP (8-Br-cGMP) onto neurones in the ventrobasal and lateral geniculate nuclei of the thalamus in anaesthetised rats, and compared its effects with those of a nitric oxide donor. 8-Br-cGMP enhanced the responses of neurones to iontophoretically applied NMDA and AMPA. Furthermore, somatosensory and visual responses of ventrobasal and lateral geniculate neurones were enhanced to 274+/-76% and 217+/-69% of control values, respectively. These effects were similar to those seen with nitric oxide donors in this study and previous work from this laboratory. When applied to thalamic neurones in an in vitro slice preparation, 8-Br-cGMP caused a membrane depolarisation associated with a decrease in input resistance. These findings indicate that activation of guanylate cyclase can cause a membrane depolarisation of thalamic neurones in vitro, and that this effect is sufficient to enhance action responses to ionotropic glutamate receptor stimulation via either exogenous agonists or sensory stimulation.
Shaw
P J
PJ
Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Charles
S L
SL
Salt
T E
TE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005074:Evoked Potentials, Visual / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005829:Geniculate Bodies / Q000166:cytology*; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D020030:Nitric Oxide Donors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008981:Molsidomine; D006162:Guanylate Cyclase; D006152:Cyclic GMP