Comparison of contractions to serotonin, carbamylcholine and prostaglandin F2 alpha in rat stomach fundus.
Contractile effects of serotonin were compared to those of carbamylcholine and prostaglandin (PG) F2 alpha in an effort to characterize serotonergic receptor activation in rat stomach fundus. All three agents elicited concentration-dependent contractions of fundal strips with serotonin (EC50 = 2 X 10(-10) M) being approximately 100-fold more potent than carbamylcholine (EC50 = 2 X 10(-8) M) and PGF2, (EC50 = 10(-8) M). The calcium channel blockers, diltiazem (5 X 10(-7) to 5 X 10(-5) M) and nitrendipine (10(-8) to 10(-5) M), attenuated responses markedly to serotonin and PGF2 alpha whereas having only minimal effects on carbamylcholine-induced contractions. Neither serotonin (10(-11) to 10(-5) M) nor PGF2 alpha (10(-9) to 10(-5) M) altered [3H]inositol monophosphate generation in fundus whereas carbamylcholine (10(-6) to 10(-5) M) increased significantly [3H]inositol monophosphate with 10(-5) M eliciting an 8-fold increase. Strips of fundus contracted submaximally with either serotonin, PGF2 alpha or carbamylcholine were compared for sensitivity to relaxants. Pinacidil (10(-8) to 10(-5) M) was equipotent (EC50 = 0.1 microM) in relaxing serotonin- and PGF2 alpha-contracted tissues. In contrast, pinacidil was 10-fold less potent in relaxing contractions produced by carbamylcholine. Likewise, nitroglycerin (10(-8) to 10(-4) M) and isoproterenol (10(-12) to 10(-7) M) were at least 10-fold more potent in relaxing serotonin- and PGF2 alpha- than carbamylcholine-induced contractions. Thus, in rat fundus, contractions associated with increased phosphoinositide hydrolysis may be more resistant to relaxation than are contractions not associated with altered phosphoinositide hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Secrest
R J
RJ
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana.
Schoepp
D D
DD
Cohen
M L
ML
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009568:Nitrendipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D020110:Pinacidil; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*
D006146:Guanidines; D010716:Phosphatidylinositols; D012701:Serotonin; D020110:Pinacidil; D002217:Carbachol; D009568:Nitrendipine; D015237:Dinoprost; D004110:Diltiazem; D005996:Nitroglycerin; D007545:Isoproterenol