Role of histamine in controlling gastric acid secretion: Histamine in an amino acid derivative, it formed continually in small amount in gastric mucosa,either in response to acid in the stomach or for other reasons, this amount, acting by itself,causes little acid secretion, however, whenever Ach, & gastrine stimulate the pariatal cells at the same time, then even small amount of histamine greatly enhance scid secretion, when the action of histamine is blocked by antihistaminic drug like cimetidine, neither Ach, nor gastrine can cause significant amount ofd acid secretion, thus histamine is necessary cofacter for exciting acid secretion

SO Multiplicative effect of Ach,,gastrine &histamin in stimulating acid secretion because no one of the 3 primary stimulater for acid secretion is effective in causing secretion of more than slight amount of acid when function alone. Regulation of pepsinogen secretion : Occures in response to 2 signals 1- stimulation of peptic cells by Ach released from vagus nerve or other enteric nerve. 2- stimulation of peptic secretion in response to acid in stomach. Gastrin released during acid secretion has an additional direct effect in stimulating peptic cell, so that the rate of secretion of pepsinogene is influanced by amount of acid in stomach.

Feed back inhibition of gastric secretion by excess acid : When gastric acidity increase (PH below 3)the gastrin mechanism for stimulating gastric acid secretion become blocked, this result from 2 factors: 1- greatly enhanced acidity depress or block the secretion of gastrin itself by G cell 2- the acid cause inhibitory nervous reflex, that inhibit gastric secretion. This feedback inhibition of gasric glands plays important role in protecting stomach against excessive acidity which promote peptic ulceration, also it is important in maintaining optimal PH for function of pep[tic enzyme in the digestive process (PH about 8)

Phases of gastric secretion : 1- cephalic phase : Occur even before food enters the stomach, it result from sight, smell, thought,or taste of food, neurogenic signals that originate in the cerebral cortex or in appetite center of hypothalamus trasmitted directly to the stomach, this phase account about 20%of gastric secretion 2- gastric phase : The local enteric reflex & gastrin mechanism causes secretion of gastric juice that continues several hours that the food remains in the stomach, this phase account 70% of gastric secretion

3- intestinal phase : The presence of food in upper S.I (particularly the duodenum) cause the stomach to secret small amount of gastric juice, probably because of release small amount of gastrin by the duodenal mucosa in response to distention, or chemical stimului, as well as several other hormones.

Inhibition of gastric secretion by intestinaL facters : Although chyme stimulate gastric secretion during intestinal phase, it paradoxically often inhibit secretion during gastric phase this result from: 1- presence of food in S.I intiate local enterogastric reflex transmitted through enterc system as well as through extrinsic sympathetic & vagus nerve that inhibit stomach secretion, this reflex intiated by distention of S.I. presence of acid, protein breakdown products

2- presence of acid, fat, protein breack down products, hyper or hypo-osmottic fluid or any irritating factors in the upper S.I cause the release of several intestinal hormones, one of these is secretin. The functional importance of inhibition of gastric secretion by intestinal factors is probably to slow the release of chyme from stomach when the S.I.is already filled, in fact the enterogastric reflex & these inhibitory hormones usually reduce stomach motility, at the same time reduces gasric sectretion.,