Binding of somatostatin to pancreatic acinar cells

Abstract

The binding of 125I-[Tyr11]somatostatin to guinea pig pancreatic acini was saturable and temperature, protein, and radioligand concentration dependent. Dissociation rate was very slow (t1/2 = 193 +/- 24 min). Scatchard analysis revealed a single class of binding sites with a Kd of 0.28 +/- 0.02 nM and a maximal binding capacity of 72 +/- 10.6 fmol/mg prot. There was a strong correlation between binding capacity and extracellular calcium concentration. Incubating acini in EGTA-containing medium with no added Ca2+ caused a 50% decrease in maximal binding capacity with a decrease in receptor affinity. Furthermore, in the absence of calcium, bound somatostatin was rapidly released (t1/2 = 14 +/- 1 min). Subcellular fractionation studies and acid treatment of acini incubated with the tracer showed that most of the somatostatin binding sites were located on the cell surface. Agents that altered cellular calcium in pancreatic acini, such as analogues of cholecystokinin and cholinergic agents, also inhibited the binding of 125I-[Tyr11]somatostatin by a calcium-dependent process. We conclude that somatostatin binds to specific plasma membrane receptors to form a slowly reversible complex that is highly reactive with calcium. Cell calcium-mobilizing agents decrease the affinity of acinar somatostatin receptors for somatostatin.

Bombesin induces a reduction of somatostatin inhibition of adenylyl cyclase activity, Gi function, and somatostatin receptors in rat exocrine pancreas

“…The parameters of the SS receptors in the control rats were similar to those previously reported by others [12,42,47,48]. Although five SS receptor subtypes have been cloned [22], the exocrine pancreas appears to express only receptor subtype 2 (SSTR2) [5].…”

“…SS was a partial antagonist of FKstimulated AC activity in pancreatic acinar membranes, in agreement with Heisler [17]. In this respect, it is well established that the inhibition of FK-stimulated AC activity by SS in pancreatic acinar cell membranes and other cell types involves three protein components found in the plasma membrane [12,42,43,47], ie, the SS receptor, the AC catalytic unit, and the GTP binding protein G i , which couples the SS receptor to the catalytic unit. Therefore, impairment of any of these three components by bombesin could attenuate the effect of SS.…”

“…However, to date, the effect of bombesin on the postreceptor SS mechanism of action is unknown. In pancreatic acinar cells, SS receptors [12,42,46] are coupled to the adenylate cyclase (AC) enzyme system via the guanine nucleotide binding inhibitory protein G i [43]. The extent of G i modification correlates with the ability of SS to inhibit adenosine 3Ј,5Ј-cyclic monophosphate (cAMP) formation.…”

In situ binding of islet hormones in the isolated perfused rat pancreas: evidence for local high concentrations of islet hormones via the islet-acinar axis

“…SS receptors have also been shown on acinar cells [3][4][5]. To our knowledge, glucagon receptors have not been reported to occur on acinar cells.…”

“…Other islet hormones, i.e., somatostatin (SS), glucagon, and pancreatic polypeptide, are reported to suppress exocrine pancreatic function, at least in vivo [2]. Among these three peptides only SS has been proven conclusively to have specific receptors on acinar cells [3][4][5]. Histological studies have demonstrated that efferent vessels from islets go through neighbouring exocrine tissue as a fenestrated vessel or connect with surrounding acinar capillary beds (islet-acinar portal system) [6][7][8].…”