Independent endocytosis of the NK(1) and NK(3) tachykinin receptors in neurons of the rat myenteric plexus.
In the myenteric plexus of rat ileum, NK(1) and NK(3) receptors are co-located almost exclusively on neurons of a single population. This study compares endocytosis of NK(1) and NK(3) receptors in these neurons. In the absence of agonist, 26.2+/-2.8% of NK(1) receptor and 29.1+/-1.1% of NK(3) receptor was located in the cytoplasm of the neurons; the remaining receptor was on the surface. The tachykinin neurotransmitters, substance P (10 pM-10 microM) and neurokinin A (10 pM-100 microM), both induced concentration-dependent endocytosis of NK(1) and NK(3) receptors. The selective NK(1) receptor agonist, [Sar(9),Met(O(2))(11)]-substance P (1 microM), induced endocytosis of NK(1) receptor (64.2+/-1.5% in cytoplasm) but not NK(3) receptor (32.9+/-5.0%). The NK(1) receptor endocytosis was reduced by the selective NK(1) receptor antagonist, CP-99994 (100 nM), but not by the selective NK(3) receptor antagonist, SR-142801 (1 microM). The selective NK(3) receptor agonist, senktide (10 nM), induced endocytosis of NK(3) receptor (61.2+/-5.4%) but not NK(1) receptor (34.0+/-4.5%). The NK(3) receptor endocytosis was blocked by SR-142801 but not by CP-99994. We also investigated the effects of monensin, which generally blocks recycling of endocytosed receptor. In the absence or presence of exogenous agonist, monensin caused a build-up of NK(1) receptor, but not NK(3) receptor, in the cytoplasm of neurons.The results demonstrate independent, agonist-induced endocytosis of NK(1) and NK(3) receptors in neurons of the myenteric plexus of rat ileum and suggest that the mechanisms of recycling of NK(1) and NK(3) receptors differ.
Jenkinson
K M
KM
Department of Anatomy and Cell Biology, University of Melbourne, 3010, Victoria, Australia. K.Jenkinson@anatomy.unimelb.edu.au
Mann
P T
PT
Southwell
B R
BR
Furness
J B
JB
D000818:Animals; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009197:Myenteric Plexus / Q000166:cytology / Q000502:physiology*; D015288:Neurokinin A / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology
D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3; D013373:Substance P; D015288:Neurokinin A; D008985:Monensin