Opioid, 5-HT1A and alpha 2 receptors localized to subsets of guinea-pig myenteric neurons.
The expression of mu opioid, alpha 2 and 5-hydroxytryptamine1A (5-HT1A) receptors on guinea-pig myenteric neurons was determined using receptor selective agonists during intracellular recordings in vitro. Agonists known to hyperpolarize myenteric neurons by increasing potassium conductance were tested: noradrenaline and UK 14304 (alpha 2 agonists); 5-HT, 8-hydroxydipropylaminotetralin, 5-carboxamidotryptamine (5-HT1A agonists); normorphine, [Met5]-enkephalin and D-Ala2-Phe4, Gly-ol5 enkephalin (mu agonists). The alpha 2 agonists hyperpolarized 46/67 AH cells; mu agonists hyperpolarized 11/66 AH cells and 5-HT1A agonists inhibited 28/57 AH cells. Hyperpolarizations to both alpha 2 and mu agonists were observed in 11/59 AH cells; hyperpolarizations to both alpha 2 and 5-HT1A agonists were observed in 23/49 AH cells. Hyperpolarizations mediated at alpha 2 receptors were observed in 11/54 S neurons and mu agonists hyperpolarized 17/45 S cells. alpha 2 and mu receptors were localized together on 10/43 S cells tested with receptor selective agonists. 5-HT1A-mediated hyperpolarizations were not observed in 36 S cells. Presynaptic inhibition of fast excitatory post-synaptic potentials (fast e.p.s.p.s., S neurons) was observed in all cells tested with alpha 2 agonists (n = 32); in 14/23 cells tested with 5-HT1A agonists and in 8/22 cells tested with mu agonists. Both alpha 2 and 5-HT1A agonists inhibited fast e.p.s.p.s in 15/23 cells, while alpha 2 and mu agonists both inhibited the fast e.p.s.p. in 8/21 cells. Inhibition of fast e.p.s.p.s by mu and 5-HT1A agonists occurred together in 2/19 cells. Slow non-cholinergic e.p.s.p.s were inhibited by alpha 2 agonists in 19/19 cells and by 5-HT1A agonists in 19/21 cells. alpha 2- and 5-HT1A-mediated inhibition of slow e.p.s.p.s occurred together in 12/14 cells. These data allow AH neurons to be divided into two groups: those expressing alpha 2 and 5-HT1A receptors and those expressing alpha 2 and mu receptors. alpha 2 and mu receptors coexist on S neurons which do not express 5-HT1A receptors. Terminals that release acetylcholine express either alpha 2 and mu or alpha 2 and 5-HT1A receptors, consistent with the idea that they are provided by AH cells. Terminals that release mediators of the slow e.p.s.p. express primarily alpha 2 and 5-HT1A receptors.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
J J
JJ
Galligan
R A
RA
North
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism*; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism* / Q000502:physiology; D011985:Receptors, Serotonin / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D011985:Receptors, Serotonin