Novel aspects of gastrin-induced activation of histidine decarboxylase in rat stomach ECL cells

Abstract

The ECL cells in the rat stomach respond to gastrin with secretion of histamine and activation of the histamine-forming enzyme histidine decarboxylase (HDC). In the present study, we have investigated factors that influence gastrin-induced activation of HDC. Gastrin-17 was given by continuous intravenous infusion to fasted and freely fed rats in various doses and for various periods of time. We found that: (1) ECL cells in fasted rats displayed one order of magnitude higher sensitivity to gastrin (3 h infusion) than did ECL cells in fed rats (ED 50 0.4 versus 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 fasted 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 and after 16 h in fed rats. In both groups, the activation was followed by a marked decline in the enzyme activity to almost prestimulation levels 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 activation of HDC in fed rats occurred 6 days after starting the infusion of the low gastrin dose and was two times higher than the maximum activation observed after the high gastrin dose; (3) In fasted rats the HDC mRNA level rose in response to the high gastrin dose, peaked after 8 h (twofold increase) and then returned to the prestimulation level. In fed rats the increase was slower, reaching a plateau after 24 h that lasted for 6 days (twofold increase); (4) The translation inhibitor cycloheximide blocked the activation of HDC induced by gastrin (4 h infusion of 5 nmol kg −1 h −1), while the transcription inhibitor actinomycin D, which suppressed the increase in HDC mRNA expression, did not.