An electrophysiological study on the membrane receptor-mediated action of glucocorticoids in mammalian neurons.
The action of glucocorticoids (GC) on neuronal cell membrane was studied in isolated and superfused guinea pig coeliac ganglia by the intracellular recording technique. Cortisol succinate (F) hyperpolarized the membrane potential of 47 of 179 cells and changed the cell's input resistance with a latency of less than 2 min in vitro. The effect persisted under low Ca2+/high Mg2+ superfusing condition and could be blocked by RU 38486, a competitive antagonist of GC cytosolic receptor. Cortisol-21-bovine albumin conjugant exhibited the same effect. Corticosterone (B) elicited hyperpolarization in another 15 of 83 cells, but dexamethasone (Dex) did not. Dex, however, depolarized 2 of 18 cells. Aldosterone, cholesterol and vehicle (ethyl alcohol) caused no detectable change in membrane potential. In vivo studies by iontophoretic application of steroids to hypothalamic paraventricular (PVN) neurons showed that F inhibited the unit discharges in 68 of 97 PVN neurons, and the effect could be antagonized by RU 38486. Dex excited 30 of 100 neurons. Estradiol (E) also inhibited the discharges, but this inhibition was not antagonized by RU 38486. The effect of GC on PVN neurons was also examined in hypothalamic slices including the paraventricular nucleus. B inhibited 28 of 104 units and excited 7 of 104 cells, and both effects could be antagonized by RU 38486. The threshold of inhibitory response was about 10(-7) M, which is close to the physiological level of the hormone in plasma. The results suggest that GC can act non-genomically and specifically through its membrane receptor on the neuronal surface, and that there might be a chemical similarity between the membrane receptor and the traditional cytosolic GC receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
Y Z
YZ
Department of Physiology, Second Military Medical College PLA, Shanghai, Peple's Republic of China.
Hua
S Y
SY
Wang
C A
CA
Wu
L G
LG
Gu
Q
Q
Xing
B R
BR
D000818:Animals; D005728:Ganglia, Sympathetic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000502:physiology*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid