Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells.
We studied whether a novel proadrenomedullin derived peptide was present and what was its physiological function in cultured bovine adrenal chromaffin cells. We found a high level of proadrenomedullin N-terminal 12 peptide (PAMP-12) which consists of a peptide from 9th amino acid to 20th amino acid of proadrenomedullin N-terminal 20 peptide (PAMP-20). PAMP-12 was released from the cells along with catecholamine upon stimulation of nicotinic cholinergic receptors. When PAMP-12 was added in the incubation medium, this peptide inhibited nicotinic receptor-mediated catecholamine release and influx of Na(+) and Ca(2+) into the cells. PAMP-12 did not affect catecholamine release evoked by histamine or by depolarization by high concentration of potassium. PAMP-12 also inhibited synthesis of catecholamines as well as the activation of tyrosine hydroxylase by nicotinic stimulation. Thus, PAMP-12 is an endogenous peptide that regulates release and synthesis of catecholamines by acting on nicotinic cholinergic receptors in an autocrine manner in adrenal chromaffin cells.
Department of Pharmacology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. hkobayas@post.miyazaki-med.ac.jp
H
H
Kobayashi
R
R
Yamamoto
K
K
Kitamura
K
K
Kuwasako
S
S
Minami
T
T
Yanagita
S
S
Shiraishi
H
H
Yokoo
T
T
Eto
A
A
Wada
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D053607:Adrenomedullin / Q000031:analogs & derivatives; D000818:Animals; D000906:Antibodies; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D018679:Cholinergic Agonists / Q000494:pharmacology; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides; D011506:Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D000906:Antibodies; D002250:Carbon Radioisotopes; D002395:Catecholamines; D018679:Cholinergic Agonists; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D011978:Receptors, Nicotinic; C108283:proadrenomedullin (9-20); D053607:Adrenomedullin; D002217:Carbachol; D012964:Sodium