Effect of pentagastrin on gastric acid secretion in the totally isolated vascularly perfused rat stomach stimulated with the phosphodiesterase inhibitor isobutyl methylxanthine.

The development of a very sensitive stomach biomodel, using the totally isolated rat stomach, is reported. Pentagastrin-stimulated acid secretion in anesthetized and conscious rats was also studied, and the capacity to produce acid and the sensitivity towards pentagastrin in the different rat stomach models were compared. The secretory capacity and the sensitivity were evaluated by means of the maximal acid output (MAO) and threshold dose (TD), respectively. Conscious rats provided with gastric fistulas had a MAO of 48 +/- 6.3 mu eq/10 min and a TD of 6 micrograms/kg-h. In anesthetized rats with luminally perfused stomach MAO was reduced to 11.6 +/- 1.2 mu eq/10 min, whereas the sensitivity was increased, as indicated by a TD of 0.5 micrograms/kg-h. Totally isolated vascularly perfused rat stomachs without isobutyl methylxanthine (IMX) produced even less acid (MAO, 2.2 +/- 0.4 mu eq/10 min) without any change in demand for stimulant (TD, 0.25 micrograms/stomach-h). Addition of IMX to the vascular perfusate in the isolated stomach preparation increased the MAO to 8.0 +/- 1.0 mu eq/10 min and induced a remarkable reduction in demand for stimulant, with a TD obtained already at a pentagastrin dose of 0.008 micrograms/stomach-h, corresponding to a concentration of pentagastrin in the vascular perfusate medium of 84.5 pM. Accordingly, the totally isolated vascularly perfused rat stomach stimulated with IMX is the most sensitive bioassay for (penta)gastrin so far reported.