Gastrin and cholecystokinin in pituitary neurons.

Abstract

Gastrins occur in the hypothalamo-hypophyseal neurons of all mammalian species examined. In addition, human, bovine, and murine hypothalamo-hypophyseal neurons contain the homologous cholecystokinins (CCKs). CCK also occurs in neurons innervating bovine melanotrophs. Al-though the concentration of gastrin is'of the same magnitude (15-30 pmol/g) in al neural lobes, the concentration of CCK varies from undetectable in pig and cat to 1 nmol/g in the cow. The constant occurrence of neurohypophyseal gastrin suggests a role different from that of the species-dependent CCK.The gut hormones gastrin and cholecystokinin (CCK) have a common origin (1) and a common COOH terminus (Trp-MetAsp-Phe-NH2), which constitutes their active site. Accordingly, they display the same spectrum of activities, although their potency towards the target organs depends on the different NH2-terminal extensions. The gastrin-CCK family of peptides possesses the same general features and specificity problems as other families of homologous peptides, like the opioid peptides and oxytocin-vasopressin peptides. Gastrin has now also been found in all lobes of the porcine pituitary (2), where its precursor, like pro-opiomelanocortin, is processed differently in corticotrophs and melanotrophs (3, 4). The porcine hypothalamo-hypophyseal system is the only known central gastrinergic neuronal system, whereas CCK is abundantly present in most remaining central nervous system regions (2-8).We now report that though gastrin is constantly present in mammalian pituitary neurons, CCK also occurs in bovine, murine, and, to a lesser extent, human hypothalamo-hypophyseal neurons. MATERIALS AND METHODSTissue Sanipli ig and Preparation. Four pools each of [8][9][10][11][12][13][14] porcine pituitaries and of 8 bovine pituitaries were obtained at a local slaughterhouse 20-30 min postmortem. They were kept on ice until dissection. Three pituitaries were obtained from pentobarbital-anesthetized cats. Three pools of 16-44 rat pituitaries were dissected immediately postmortem. Three normal human pituitaries were obtained 6-16 hr postmortem. The porcine, feline, bovine, and murine glands were dissected into anterior, intermediate, and neural lobes under a microscope (x50, final magnification). Some bovine and the human anterior and neural lobes were dissected without magnification, but only the most anterior and posterior parts, respectively, were examined to ensure absence of contamination from other lobes. Further control was achieved by measuring the vasopressin and melanocyte-stimulating hormone (MSH) concentrations in the samples. Moreover, the secretory vesicles from two pools of rat neurointermediate lobes (n = 60 and 300) and one pool of bovine neural lobes (n = 6), isolated as described (9), were examined. All of the specimens were frozen in liquid nitrogen, minced, boiled for 20 min in redistilled water (pH 6.6, 5 ml/g of tissue), homogenized, and centrifuged and the supernatants were decanted. The pellets were reextracted in 0.5 M acetic acid, homogeniz...

Cholecystokinin evokes secretion of oxytocin and vasopressin from rat neural lobe independent of external calcium.

“…In the latter tissues, L-364,718 is a very potent antagonist of CCK, and the sulfated form of CCK-8 is the preferred ligand. CCK-8 is the predominant form of CCK found in the rat neurohypophysis (16), but we have shown that the five C-terminal amino acids of CCK (Table 1) are sufficient to produce a potent secretion of the neurohypophysial hormones OT and VP.…”

Renal effects of gastrin C‐terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man

“…The C-terminal tetrapeptide of gastrin has all the biological actions of the whole molecule and is shared by cholecystokinin (CCK) (Gregory, 1974). More recently the biologically active C-terminal octapeptide of CCK (CCK8) has been found in high concentrations in brain and peripheral neurones (Rehfeld et al, 1979). Apart from its presence in myenteric nerves and in some nerves to the urogenital tract (Rehfeld, 1980), neural CCK8 has not been found in the kidney.…”

Preprocholecystokinin processing in the normal human anterior pituitary.

“…In previous studies on pituitary CCK neurons (12), CCK was also found in the human adenohypophysis. Characterization of adenohypophyseal CCK with the radioimmunoassay library (6,11) has revealed a processing pattern that suggests a role for posttranslational modifications in the differentiation of endocrine cells.…”