Differential calcium responses to the pituitary adenylate cyclase-activating polypeptide (PACAP) in the five main cell types of rat anterior pituitary.
We have compared the effects of pituitary adenylate cyclase-activating polypeptide (PACAP-27) on the five main cell types of rat anterior pituitary in primary culture by monitoring changes in cytosolic Ca2+ concentration ([Ca2+]i) in single fura-2-loaded cells. Cells were typed by multiple sequential primary immunocytochemistry at the end of the Ca2+ measurements. PACAP-27 increased [Ca2+]i by three different mechanisms, each one dominant in a given cell type. These involved Ca2+ entry or release from the stores and mediation through different second messenger pathways: (1) stimulation of Ca2+ entry mediated by cAMP was the main mechanism in somatotrophs; (2) Ca2+ release from the intracellular Ca2+ stores mediated by phospholipase C (PLC) was the dominant modality in gonadotrophs; (3) stimulation of Ca2+ entry not mediated by cAMP was the main mechanism in lactotrophs. A minor fraction of somatotrophs (11%) may also use mechanism 3. Corticotrophs and thyrotrophs exhibited weak responses to PACAP (<10% of the cells responded), which in all cases were mediated by mechanism 1. Mechanism 3 represents a novel effect of PACAP which cannot be explained by interaction with the conventional PACAP receptor families.
Alarcón
P
P
Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo, Superior de Investigaciones Científicas, Departamento de Fisiología y Bioquímica, Facultad de Medicina, Spain.
García-Sancho
J
J
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009994:Osmolar Concentration; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000378:metabolism; D010738:Type C Phospholipases / Q000502:physiology
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D000242:Cyclic AMP; D010738:Type C Phospholipases; D002118:Calcium