NONCHOLINERGIC NEUROTRANSMISSION IN THE GUINEA PIG INFERIOR MESENTERIC GANGLION: A SENSORY ROLE IN GASTROINTESTINAL PHYSIOLOGY (SYMPATHETIC, SLOW EPSP, PREVERTEBRAL, VASOPRESSIN, SUBSTANCE P).
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AbstractNoncholinergic neurotransmission was studied in vitro in the guinea pig inferior mesenteric ganglion (IMG) using the technique of intracellular recording. First, the role of substance P (SP) in noncholinergic transmission was examined. Forty-four percent of IMG neurons depolarized upon superfusion of SP (1-10 x 10⁻⁷M); however, some neurons that were insensitive to SP still exhibited slow excitatory potentials (EPSPs) in response to nerve stimulation. During exposure to SP, slow EPSPs were depressed by 52% compared to paired control EPSPs. In animals treated with systemic doses of capsaicin (50-350 mg/kg), mean slow EPSP amplitude was 3.5 mV compared to 6.8 mV in untreated animals. Arginine-vasopressin (AVP) was tested for its electrophysiological effects on IMG neurons and synaptic transmission. AVP (0.5-10 x 10⁻⁷M) produced a depolarization in 67% of neurons, accompanied by an increase in membrane resistance of 44%. The depolarizations and increase in resistance were blocked by a specific V₁ receptor antagonist. During AVP-induced depolarizations, slow EPSPs were reversibly depressed in the majority of neurons by a mean of 71% relative to paired control EPSPs. The V₁ antagonist blocked slow EPSPs in only 10% of neurons tested. A group of neurons exhibiting slow EPSPs was exposed separately to both AVP and SP. Some neurons were exclusively sensitive to either SP or AVP, others were sensitive to both peptides, and still others were sensitive to neither peptide. The physiologic role of noncholinergic transmission was examined using a preparation consisting of a segment of distal colon attached to the IMG. Distension of the colon segment produced a slow depolarization resistant to cholinergic antagonists in 44% of IMG neurons. Distension-induced noncholinergic depolarizations increased in amplitude with colonic intraluminal pressure and with membrane hyperpolarization, and were accompanied by an increase in membrane input resistance of 21%. Capsaicin in vivo reduced the number of neurons exhibiting the noncholinergic mechanosensory depolarization, and in vitro capsaicin and SP desensitization reduced the amplitude of the depolarization. These results suggest that (1) both SP and AVP may be transmitters of noncholinergic potentials in the IMG, (2) some IMG neurons receive heterogeneous peptidergic innervation, and (3) noncholinergic transmission in the IMG is involved in sensory regulation of visceral autonomic function.
Degree ProgramPharmacology and Toxicology