title: Receptor subtypes: species variations in secretin affect potency for pancreatic but not gastric secretion.
abstract: 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.
authors.affiliation: CURE Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, and Digestive Diseases Division, UCLA School of Medicine, Los Angeles, California 90073, USA.
authors.forename: Travis E
authors.initials: TE
authors.lastname: Solomon
authors.forename: David A
authors.initials: DA
authors.lastname: Keire
authors.forename: Peixian
authors.initials: P
authors.lastname: Gong
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zong
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Reeve
mesh_terms: 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
chemical_list: D005755:Gastrins; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin