Receptor subtypes: species variations in secretin affect potency for pancreatic but not gastric secretion.
BACKGROUND
Receptor subtypes can be distinguished by different actions of agonists on physiologic responses. In this study, we compared effects of four species variants of secretin (rat, porcine, canine, and human) on pancreatic secretion and gastrin-induced acid secretion in urethane-anesthetized rats. These secretins differ by one to three residues in position 14, 15, or 16 and were used to probe for the presence of different secretin receptor subtypes in the rat.


METHODS
Pancreatic responses were measured in a two-point parallel line bioassay with porcine secretin (3 and 30 pmol/kg IV bolus) as standard. Inhibition of gastric acid secretion by each secretin (100 pmol/[kg x h]) was quantitated against a threshold dosage of gastrin-17 (200 pmol/[kg x h]), and percent inhibition of incremental acid responses was determined.


RESULTS
Rat secretin was significantly more potent than other secretins for pancreatic secretion, in the order of rat > porcine > canine > human. The four secretins significantly inhibited gastrin-induced acid secretion by 37% to 49%, with no statistically significant differences among the forms.


CONCLUSIONS
Stimulation of pancreatic secretion was influenced by species variations in secretin structure, but inhibition of gastric acid secretion was not. This finding suggests that secretin receptor subtypes with different recognition patterns mediate these responses.
Solomon
Travis E
TE
CURE Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, and Digestive Diseases Division, UCLA School of Medicine, Los Angeles, California 90073, USA.
Keire
David A
DA
Gong
Peixian
P
Zong
Yumei
Y
Reeve
Joseph R
JR
D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000145:classification* / Q000502:physiology; D012633:Secretin / Q000737:chemistry* / Q000494:pharmacology*; D016415:Sequence Alignment; D013045:Species Specificity; D013552:Swine
D005755:Gastrins; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin