Opposing roles for D-1 and D-2 dopamine receptors in the regulation of lower esophageal sphincter motility in the rat

Life Sci. 1994;54(15):1035-45. doi: 10.1016/0024-3205(94)00414-5.

Abstract

In the present study we have identified biochemically DA receptors in rat Lower Esophageal Sphincter (LES) and have identified their role in the control of the sphincter motility. Dopamine (DA) both stimulated and inhibited cyclic AMP formation in rat LES; the pharmacological characterization of these effects indicated that they were mediated by D-1 and D-2 receptors, respectively. The results obtained with LES helical strips showed that DA plays both inhibitory and stimulatory effects on the sphincter function; the pharmacological characterization with selective D-1 and D-2 agonists and antagonists strongly suggested that D-1 receptors are involved in LES contraction, while D-2 receptors mediate the relaxation of the sphincter. The same results were obtained by measuring intraluminal LES pressure in anesthetized rats. The selective D-1 agonist fenoldopam (40 micrograms/kg, i.v.) increased the LES pressure; on the other hand bromocriptine (10 micrograms/kg, i.v.), which preferentially interacts with D-2 receptors, induced a decrease of the resting LES pressure.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / analogs & derivatives
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Animals
  • Benzazepines / pharmacology
  • Bromocriptine / pharmacology
  • Dihydroergotoxine / pharmacology
  • Dopamine / pharmacology
  • Dopamine Agents / pharmacology
  • Ergolines / pharmacology
  • Esophagogastric Junction / chemistry
  • Esophagogastric Junction / physiology*
  • Fenoldopam
  • In Vitro Techniques
  • Male
  • Peristalsis / physiology
  • Phentolamine / pharmacology
  • Prazosin / pharmacology
  • Quinpirole
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / analysis
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Dopamine D2 / analysis
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / physiology*

Substances

  • Benzazepines
  • Dopamine Agents
  • Ergolines
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Dihydroergotoxine
  • Quinpirole
  • Bromocriptine
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Fenoldopam
  • Dopamine
  • Prazosin
  • Phentolamine