Inhibition of voltage-dependent calcium channels by prostaglandin E2 in rat melanotrophs.
The effects of PGE2 on voltage-dependent Ca2+ channel currents were studied in dissociated rat melanotrophs by the whole-cell configuration of the patch-clamp technique. In about 90% of melanotrophs examined, PGE2 reversibly inhibited voltage-dependent Ba2+ currents elicited by voltage steps from a holding potential of -80 to 0 mV, with an ED50 of 68 nM. The maximum inhibition of Ba2+ currents by 1 microM PGE2 (35.3%) was comparable with that by the maximally effective concentration (100 nM) of dopamine. The EP1/EP3 PGE (EP) agonists, 17PT-PGE2 and sulprostone, and the EP2/EP3 agonist, misoprostol, mimicked the inhibition by PGE2, whereas the selective EP2 agonist, butaprostol, had little effect. The inhibition by PGE2 was partially, but significantly, reduced by the selective EP1 antagonist, SC-51322. The magnitude of the PGE2-induced inhibition of Ba2+ currents was greatly reduced by pretreatment with pertussis toxin, or by a depolarizing prepulse, to +80 mV, lasting for 50 msec. Although four distinct types (N-, P/Q-, L-, and R-types) of high-threshold Ba2+ currents were observed, PGE2 (1 microM) caused significant inhibition of only P/Q- and L-type currents, which were 17.3 and 10.1%, respectively, of the total Ba2+ currents. These results suggest that PGE2 inhibits P/Q- and L-type Ca2+ channels of rat melanotrophs via EP1 and EP3 receptors, which are coupled to pertussis toxin-sensitive G proteins, and produces both voltage-sensitive and -insensitive inhibition of Ca2+ channels.
Tanaka
K
K
Department of Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Shibuya
I
I
Kabashima
N
N
Ueta
Y
Y
Yamashita
H
H
D000818:Animals; D001464:Barium / Q000037:antagonists & inhibitors / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000096:biosynthesis; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011458:Prostaglandins E / Q000819:agonists / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011458:Prostaglandins E; D010566:Virulence Factors, Bordetella; D001464:Barium; D009074:Melanocyte-Stimulating Hormones; D037342:Pertussis Toxin; D015232:Dinoprostone