NOVEL ASPECTS OF GASTRIN-INDUCED ACTIVATION OF HISTIDINE-DECARBOXYLASE IN RAT STOMACH ECL CELLS

The ECL cells in the rat stomach respond to gastrin with secretion of histamine and activation of the histamine-forming enzyme histidine dec arboxylase (HDC). In the present study, we have investigated factors t hat influence gastrin-induced activation of HDC. Gastrin-17 was given by continuous intravenous infusion to fasted and freely fed rats in va rious doses and for various periods of time. We found that: (1) ECL ce lls in fasted rats displayed one order of magnitude higher sensitivity to gastrin (3 h infusion) than did ECL cells in fed rats (ED50 0.4 ve rsus 4.0 nmol kg(-1) h(-1)), while the maximum response to gastrin was two times greater in fed rats than in fasted rats; (2) HDC in both fa sted and fed rats responded to a high gastrin dose (5 nmol kg(-1) h(-1 )) in a biphasic manner with peak activity after 8 h in fasted rats an d after 16 h in fed rats. In both groups, the activation was followed by a marked decline in the enzyme activity to almost prestimulation le vels 24 h after start of the infusion. A low gastrin dose (0.4 nmol kg (-1) h(-1)) did not induce such a biphasic response. Maximum activatio n of HDC in fed rats occurred 6 days after starting the infusion of th e low gastrin dose and was two times higher than the maximum activatio n observed after the high gastrin dose; (3) In fasted rats the HDC mRN A level rose in response to the high gastrin dose, peaked after 8 h (t wofold increase) and then returned to the prestimulation level. In fed rats the increase was slower, reaching a plateau after 24 h that last ed for 6 days (twofold increase); (4) The translation inhibitor cycloh eximide blocked the activation of HDC induced by gastrin (4 h infusion of 5 nmol kg(-1) h(-1)), while the transcription inhibitor actinomyci n D, which suppressed the increase in HDC mRNA expression, did not. (C ) 1998 Elsevier Science B.V. All rights reserved.