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 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 acetycholine 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.