Subunit composition of G(o) proteins functionally coupling galanin receptors to voltage-gated calcium channels.
The neuropeptide galanin is widely expressed in the central nervous system and other tissues and induces different cellular reactions, e.g. hormone release from pituitary and inhibition of insulin release from pancreatic B cells. By microinjection of antisense oligonucleotides we studied the question as to which G proteins mediate the galanin-induced inhibition of voltage-gated Ca2+ channels in the rat pancreatic B-cell line RINm5F and in the rat pituitary cell line GH3. Injection of antisense oligonucleotides directed against alpha 01, beta 2, beta 3, gamma 2 and gamma 4 G protein subunits reduced the inhibition of Ca2+ channel current which was induced by galanin, whereas no change was seen after injection of cells with antisense oligonucleotides directed against alpha i, alpha q, alpha 11, alpha 14, alpha 15, beta 1, beta 4, gamma 1, gamma 3, gamma 5, or gamma 7 G protein subunits or with sense control oligonucleotides. In view of these data and of previous results, we conclude that the galanin receptors in GH3 and in RINm5F cells couple mainly to the G(0) protein consisting of alpha 01 beta 2 gamma 2 to inhibit Ca2+ channels and use alpha 01beta 3 gamma 4 less efficiently. The latter G protein composition was previously shown to be used by muscarinic M4 receptors to inhibit Ca2+ channels.
Kalkbrenner
F
F
Institut für Pharmakologie der Freien Universität Berlin, Germany.
Degtiar
V E
VE
Schenker
M
M
Brendel
S
S
Zobel
A
A
Heschler
J
J
Wittig
B
B
Schultz
G
G
D000595:Amino Acid Sequence; D000818:Animals; D017609:Barium Compounds / Q000378:metabolism; D001483:Base Sequence; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus; D002712:Chlorides / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019004:Galanin / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D008845:Microinjections; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology; D016376:Oligonucleotides, Antisense; D010902:Pituitary Gland / Q000166:cytology / Q000502:physiology; D051381:Rats; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000502:physiology*
D017609:Barium Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002712:Chlorides; D018721:Muscarinic Agonists; D016376:Oligonucleotides, Antisense; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; C024986:barium chloride; D019004:Galanin; D002217:Carbachol; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go