Electrophysiological studies on the interaction of 5-hydroxytryptamine with sympathetic transmission in the guinea pig inferior mesenteric artery and ganglion.
The interaction of 5-hydroxytryptamine (5-HT) with sympathetic transmission was investigated in the guinea pig inferior mesenteric artery (IMA) and ganglion (IMG). Intracellular recordings of membrane potential were made using glass microelectrodes. Superfusion of 5-HT (0.3 microM) reduced the amplitudes of stimulation-evoked excitatory junction potentials in the IMA. 5-HT had no effect on depolarizing responses to pressure-ejection of adenosine triphosphate or norepinephrine in the IMA. The inhibitory effect of 5-HT on excitatory junction potentials in the IMA was abolished by methysergide (3 microM), but was unaffected by the following antagonists: methiothepin (1 microM), MDL 72222 (3 microM), MDL 11939 (0.3 microM) or by phentolamine (10 microM). In the IMG, pressure-ejection of 5-HT (10 mM) evoked fast and slow depolarizing responses in 77% of neurons tested; the fast depolarizing responses to 5-HT were reduced in the presence of MDL 72222 (5 microM). Superfusion of 5-HT (0.3-3 microM) had no effect on stimulation-evoked fast excitatory postsynaptic potentials in the IMG. Thus, the results of the present study suggest that, depending on its site of interaction with postganglionic sympathetic neurons, 5-HT may have excitatory or inhibitory effects on sympathetic transmission. 5-HT may inhibit transmitter release through the activation of as yet unidentified 5-HT receptors on the sympathetic nerve endings in mesenteric blood vessels. Whereas, in the prevertebral ganglion, 5-HT may act to facilitate sympathetic transmission, in part, through activation of 5-HT3, receptors on the somata of principal neurons.
Meehan
A G
AG
Department of Pharmacology, College of Medicine, University of Arizona, Tucson.
Kreulen
D L
DL
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation* / Q000648:ultrastructure; D008719:Methiothepin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014326:Tropanes / Q000494:pharmacology
D010880:Piperidines; D012702:Serotonin Antagonists; D014326:Tropanes; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol; D012701:Serotonin; D008719:Methiothepin; C042253:bemesetron; D008784:Methysergide; D010646:Phentolamine