5-hydroxytryptamine decreases somatostatin receptors and somatostatin-responsive adenylyl cyclase in rat pancreatic acinar membranes.
Pretreatment of pancreatic acini with 5-hydroxytryptamine (5-HT) reduced the binding of the labeled somatostatin (SS) analogue 125I-Tyr3-SMS to pancreatic acinar membranes. This effect was dependent of the dose of 5-HT used and length of pretreatment. This inhibitory effect of 5-HT was abolished when pancreatic acini were pretreated with 5-HT in the presence of the 5-HT1p receptor-antagonist 5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP). Pretreatment of pancreatic acini with 5-HT reduced the inhibition by the stable SS analogue SMS 201-995 of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity in pancreatic acinar membranes. There was no statistical difference established between IC50 values for the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) which inhibits ligand binding to SMS receptors in controls and in 5-HT treated pancreatic cells, respectively. In addition, no significant differences were seen in the level of Gi proteins in the control and 5-HT treated pancreatic acini. These data suggest that the decrease of the number of 125I-Tyr3-SMS receptors, would explain the decreased sensitivity of AC to SMS 201-995 in membranes from 5-HT-pretreated acini.
Muñoz-Acedo
G
G
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain.
Rodríguez-Martin
E
E
Puebla
L
L
Arilla
E
E
D000818:Animals; D001665:Binding Sites; D019204:GTP-Binding Proteins / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D015282:Octreotide / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*
D017481:Receptors, Somatostatin; D012701:Serotonin; D006165:Guanylyl Imidodiphosphate; D013004:Somatostatin; D019204:GTP-Binding Proteins; D015282:Octreotide