Somatostatin receptors on canine fundic D-cells: evidence for autocrine regulation of gastric somatostatin.
Somatostatin is known to have inhibitory effects on the release and action of a wide variety of gut peptides. Previous studies in vivo have suggested a potential inhibitory role for somatostatin even on its own secretion. To determine whether this autoregulatory effect is the result of a direct action of the peptide on the cell that is responsible for its secretion, we examined the effect of a non-immunoreactive but biologically active analogue of somatostatin ([Leu8-D-Trp22-Tyr25]S28) on release of somatostatin-like immunoreactivity (SLI) from isolated canine fundic D-cells. We identified somatostatin binding sites with dissociation constants of 1.2 X 10(-9) and 3.8 X 10(-8) M that coenriched with D-cells. Somatostatin 14, somatostatin 28, and [Leu8-D-Trp22-Tyr25]S28 were equivalent in displacing 125I-[Leu8-D-Trp22-Tyr25]S28 from the binding sites. [Leu8-D-Trp22-Tyr25]S28 inhibited SLI release from D-cells stimulated with (DBcAMP), and pentagastrin. Pertussis toxin pretreatment prevented the inhibitory effects of [Leu8-D-Trp22-Tyr25]S28 on both SLI secretion and cAMP accumulation by on both SLI secretion and cAMP accumulation by D-cells stimulated with epinephrine and forskolin. In contrast, [Leu8-D-Trp22-Tyr25]S28 inhibition of SLI release induced by DBcAMP and pentagastrin was not altered by pertussis toxin. Our data suggest that somatostatin autoregulates its own secretion via specific receptors on D-cells. This inhibitory effect is mediated by mechanisms that are both dependent on and independent of pertussis toxin-sensitive inhibitory guanine nucleotide binding proteins.
Park
J
J
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0362.
Chiba
T
T
Yokotani
K
K
DelValle
J
J
Yamada
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005748:Gastric Fundus / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010418:Pentagastrin / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D017481:Receptors, Somatostatin; D015398:Signal Transduction; D013004:Somatostatin / Q000502:physiology*
D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D005576:Colforsin; D013004:Somatostatin; D003994:Bucladesine; D010418:Pentagastrin; D004837:Epinephrine