Pituitary adenylate cyclase-activating polypeptide releases 7B2, adrenocorticotrophin, growth hormone and prolactin from the mouse and rat clonal pituitary cell lines AtT-20 and GH3.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from ovine hypothalami and so called because of its ability to stimulate pituitary adenylate cyclase activity. Alternative amidation and proteolytic processing of prepro-PACAP gives rise to two bioactive-amidated forms, PACAP-NH2(1-38) (PACAP-38) and PACAP-NH2(1-27) (PACAP-27). 7B2 is a polypeptide of 185 amino acids which is predominantly found in secretory granules and is widely distributed in rat and human tissues. We investigated the ability of the two forms of PACAP to stimulate GH, prolactin and 7B2 release by the rat pituitary clonal cell line GH3, and ACTH and 7B2 by the mouse pituitary clonal cell line AtT-20. PACAP-38 and PACAP-27 stimulated 7B2 and GH/prolactin or ACTH secretion with a similar efficacy over the 2-h incubation period from GH3 and AtT-20 cells respectively. 7B2 secretion was also stimulated by corticotrophin-releasing factor (CRF-41) and vasoactive intestinal polypeptide (VIP) in AtT-20 cells, and thyrotrophin-releasing hormone (TRH) and VIP in GH3 cells. Addition of PACAP to CRF-41 resulted in an additive effect on ACTH secretion and a synergistic effect on 7B2 secretion in AtT-20 cells. No synergism was observed when PACAP was added together with TRH, either on GH and prolactin secretion or on 7B2 release from GH3 cells. PACAP-mediated 7B2 secretion from both cell lines and PACAP-stimulated ACTH release from AtT-20 cells were reduced by 5 mg octapeptide synthetic somatostatin analogue/l (5 mg SMS 201-995/l).
Propato-Mussafiri
R
R
Department of Medicine, Royal Postgraduate Medical School, London.
Kanse
S M
SM
Ghatei
M A
MA
Bloom
S R
SR
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004357:Drug Synergism; D013006:Growth Hormone / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D009479:Neuropeptides / Q000494:pharmacology*; D015282:Octreotide / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D012756:Sheep / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010907:Pituitary Hormones; C497680:Scg5 protein, rat; D014660:Vasoactive Intestinal Peptide; D013973:Thyrotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D015282:Octreotide