Characterization of receptors mediating the effects of dopamine on gastric smooth muscle.
The effects of dopamine on circular and longitudinal smooth muscle from the body of the guinea pig stomach were examined. In circular muscle, dopamine (10(-6)-10(-3) mol/L) induced contractions that were tetrodotoxin-insensitive with a concentration of half-maximal effect (EC50) of 6.3 x 10(-6) mol/L for dopamine vs. 1.4 x 10(7) mol/L for norepinephrine. The efficacies of dopamine- and norepinephrine-induced contraction were similar. The alpha-adrenoceptor antagonist phentolamine competitively inhibited dopamine-induced circular contractions (Ki = 2.5 x 10(-8) mol/L slope 1.06), whereas the dopamine antagonist haloperidol had no effect. The alpha 1-antagonist prazosin competitively inhibited dopamine-induced contractions (Ki = 1.8 x 10(-8) mol/L, slope 1.03), whereas the alpha 2 antagonist yohimbine was slightly less potent (Ki = 2.2 x 10(-7) mol/L, slope 1.15). In longitudinal muscle, dopamine produced relaxation with an EC50 of 2.9 x 10(-5) mol/L vs. 2.4 x 10(-6) mol/L for norepinephrine. Tetrodotoxin reduced relaxation to dopamine by one third at low doses of dopamine (10(-5)-10(-4) mol/L) and had no effect above 10(-3) mol/L. Phentolamine did not inhibit dopamine-induced relaxation, whereas haloperidol demonstrated potent competitive inhibition (Ki = 5.8 x 10(-7) mol/L, slope 0.90). The selective DA1 antagonist Sch 23390 (Research Biochemicals Inc., Natick, MA) showed competitive antagonism (Ki = 6.3 x 10(-6) mol/L, slope 0.98), whereas the selective DA2 antagonist domperidone had no effect. The effect of Sch 23390 was tetrodotoxin resistant. It is concluded that in the body of the guinea pig stomach, dopamine induces contraction in circular muscle through smooth muscle alpha adrenoceptors, whereas in longitudinal muscle, dopamine induces relaxation through smooth muscle DA1 receptors.
Kurosawa
S
S
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Hasler
W L
WL
Torres
G
G
Wiley
J W
JW
Owyang
C
C
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013270:Stomach / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D018492:Dopamine Antagonists; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D013779:Tetrodotoxin; D004298:Dopamine; D009638:Norepinephrine