Histamine receptors on submucous neurons in guinea pig colon

1993 ◽  
Vol 264 (1) ◽  
pp. G74-G80 ◽  
Author(s):  
T. Frieling ◽  
H. J. Cooke ◽  
J. D. Wood

Intracellular microelectrodes were used to investigate the actions of histamine in the submucous plexus of the distal colon of the guinea pig. Three effects resulted from application of histamine to submucous neurons. The first was membrane depolarization associated with increased input resistance and augmented excitability. The second was presynaptic suppression of acetylcholine release at nicotinic synapses. The third occurred during long-term application and consisted of recurrent trains of action potentials associated with periodic depolarization of membrane potential. Pharmacological analysis, with selective agonists and antagonists, suggested mediation of the first and third response by postsynaptic histamine H2 receptors. The second response was mediated by presynaptic histamine H3 receptors. These actions of histamine represent a mechanism for neuroimmune signaling between mucosal mast cells and submucous neurons in gastrointestinal type 1 hypersensitivity reactions to allergens.

1993 ◽  
Vol 264 (3) ◽  
pp. G442-G446 ◽  
Author(s):  
D. H. Zafirov ◽  
H. J. Cooke ◽  
J. D. Wood

Slow synaptic excitation and inhibition were studied with intracellular microelectrodes in submucous ganglion cells of the guinea pig ileum. Elevation of adenosine 3',5'-cyclic monophosphate (cAMP) after application of forskolin or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) resulted in slowly activating depolarization of the membrane potential. The depolarization was associated with increased input resistance, enhanced excitability, and suppression of hyperpolarizing afterpotentials. This occurred in AH/type 2 but not S/type 1 neurons. The action of forskolin or IBMX mimicked slow synaptic excitation in the same neurons. Focal electrical stimulation also evoked slow inhibitory postsynaptic potentials (IPSPs). The amplitude and duration of the IPSPs were increased by forskolin or a membrane-permeant analogue of cAMP. Treatment with phentolamine, yohimbine or idazoxan suppressed the IPSPs before and after potentiation by forskolin, suggesting that the IPSPs were mediated by release of norepinephrine acting at alpha 2-adrenoceptors. Application of adenosine or selective adenosinergic A1 agonists suppressed or abolished the IPSPs. The results suggest that elevation of cAMP facilitates the release of norepinephrine at alpha 2-synapses on submucous neurons of guinea pig small bowel.


1991 ◽  
Vol 260 (6) ◽  
pp. G842-G849 ◽  
Author(s):  
T. Frieling ◽  
H. J. Cooke ◽  
J. D. Wood

Intracellular electrical recording was used to investigate synaptic behavior of ganglion cells in the neural networks of the submucosal plexus of the guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs), mediated by nicotinic receptors, were found in all S/type 1 neurons, 70% of AH/type 2, 75% of type 3, and 95% of type 4 neurons. Slow EPSPs were characterized by membrane depolarization, increased input resistance, enhanced action potential discharge, and suppression of hyperpolarizing afterpotentials in 64% of the S/type 1 neurons, 74% of AH/type 2, 31% of type 3, and 70% of type 4 neurons. Micropressure application of acetylcholine evoked a two-component depolarizing response consisting of an initial transient with decreased input resistance followed by a prolonged depolarization associated with increased input resistance. The transient response was suppressed by nicotinic-blocking drugs. Muscarinic antagonists suppressed the prolonged response. Acetylcholine acted also at presynaptic muscarinic receptors to suppress stimulus-evoked fast EPSPs. No stimulus-evoked inhibitory synaptic potentials were observed. Norepinephrine, applied by microejection, acted at alpha 2-adrenoceptors to hyperpolarize the membrane potential in association with decreased neuronal input resistance.


1988 ◽  
Vol 254 (4) ◽  
pp. G522-G530 ◽  
Author(s):  
P. R. Wade ◽  
J. D. Wood

Intracellular recording was used in vitro to analyze electrophysiological properties of neurons in myenteric ganglia of guinea pig distal colon. The neurons were classified into six types based on their electrical behavior. Type 1 colonic neurons discharged action potentials throughout depolarizing current pulses and were otherwise similar to S/type 1 neurons found in the guinea pig small bowel. The second type had passive and active electrical properties similar to those of AH/type 2 myenteric neurons of the small intestine. These cells discharged only a single spike at the onset of depolarizing current pulses, and the spikes were followed by long-lasting hyperpolarizing afterpotentials. Excitability of the type 2 neurons was enhanced in the presence of elevated Mg2+ and reduced Ca2+, and the spikes were unaffected by tetrodotoxin. Type 3 colonic neurons showed fast synaptic potentials but did not generate action potentials. The majority of neurons were referred to as type 2 colonic neurons. Type 4 neurons discharged single action potentials only at the onset of depolarizing current pulses, and the spikes were not followed by prolonged hyperpolarizing afterpotentials. Unlike type 2 neurons, excitability remained unchanged in the presence of reduced extracellular Ca2+ and elevated Mg2+. Action potentials of type 4 neurons were suppressed or abolished by tetrodotoxin. A group of spontaneously active neurons was classified as type 5 colonic neurons. Type 6 cells were inexcitable and assumed to be glial cells.


1993 ◽  
Vol 264 (3) ◽  
pp. G414-G421 ◽  
Author(s):  
F. L. Christofi ◽  
J. D. Wood

Intracellular microelectrodes were used to examine the actions of pituitary adenylate cyclase-activating peptide (PACAP) on morphologically identified myenteric neurons and glial cells of the guinea pig small bowel. PACAP-27 and PACAP-38 evoked excitatory responses in 96% of after hyperpolarizing (AH)/type 2 neurons. The half-maximal concentration for PACAP-27 was 1.5 nM. The responses consisted of membrane depolarization in association with increased input resistance, suppression of hyperpolarizing afterpotentials, and repetitive spike discharge. Forskolin mimicked the action of PACAP in all AH/type 2 neurons. PACAP excited 36% of S/type 1 neurons. Most of the AH/type 2 neurons had Dogiel II morphology, whereas the S/type 1 neurons were uniaxonal with morphology characteristics of Dogiel I or filamentous neurons. No glial cells responded to PACAP. A selective A1 adenosine receptor agonist blocked the excitatory action of PACAP, and this was reversed by a selective A1 antagonist. The results suggest that excitatory PACAP receptors and inhibitory adenosine A1 receptors are linked to adenylate cyclase in AH/type 2 myenteric neurons.


1988 ◽  
Vol 255 (2) ◽  
pp. G184-G190 ◽  
Author(s):  
P. R. Wade ◽  
J. D. Wood

Intracellular recording methods were used in vitro to analyze the synaptic behavior of neurons in myenteric ganglia of guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs) were observed in a variety of types of colonic neurons. Both spontaneous and stimulus-evoked EPSPs were abolished or suppressed by addition of hexamethonium, tetrodotoxin, or elevation of Mg2+ and reduction of Ca2+ in the bathing medium. Individual neurons usually received inputs from several fiber tracts and multiple EPSPs were sometimes evoked by electrical stimulation of single-fiber tracts. Stimulus-evoked fast EPSPs were always of greater amplitude, longer duration, and longer decay time than were spontaneous fast EPSPs in the same neurons. No rundown of the fast EPSPs occurred during prolonged stimulation at frequencies up to 10 Hz. Repetitive stimulation evoked slow depolarizing potentials (slow EPSPs) in 25% of the neurons. Characteristics of the slow EPSPs were 1) slow rise times, 2) duration in the seconds time domain, 3) enhanced excitability, 4) increased input resistance, and 5) reduction of hyperpolarizing after-potentials. In general, the variety of synaptic potentials and the properties of the events were the same as found in myenteric neurons of the guinea pig small bowel. Compared with synaptic behavior of small intestinal myenteric neurons, the notable differences were absence of the rundown phenomenon for fast EPSPs in the colonic neurons and a greater incidence of spontaneously occurring fast EPSPs.


2000 ◽  
Vol 278 (4) ◽  
pp. G625-G634 ◽  
Author(s):  
Yutaka Hosoda ◽  
Adi Winarto ◽  
Toshihiko Iwanaga ◽  
Atsukazu Kuwahara

The effect of ANG II on mucosal ion transport and localization of ANG type 1 receptor (AT1R) in the guinea pig distal colon was investigated. Submucosal/mucosal segments were mounted in Ussing flux chambers, and short-circuit current ( I sc) was measured as an index of ion transport. Serosal addition of ANG II produced a concentration-dependent (10− 9–10− 5M) increase in I sc. The maximal response was observed at 10− 6 M; the increase in I sc was 164.4 ± 11.8 μA/cm2. The ANG II (10− 6 M)-evoked response was mainly due to Cl− secretion. Tetrodotoxin, atropine, the neurokinin type 1 receptor antagonist FK-888, and piroxicam significantly reduced the ANG II (10− 6M)-evoked response to 28, 45, 58, and 16% of control, respectively. Pretreatment with prostaglandin E2(10− 5 M) resulted in a threefold increase in the ANG II-evoked response. The AT1R antagonist FR-130739 completely blocked ANG II (10− 6M)-evoked responses, whereas the ANG type 2 receptor antagonist PD-123319 had no effect. Localization of AT1R was determined by immunohistochemistry. In the immunohistochemical study, AT1R-immunopositive cells were distributed clearly in enteric nerves and moderately in surface epithelial cells. These results suggest that ANG II-evoked electrogenic Cl−secretion may involve submucosal cholinergic and tachykinergic neurons and prostanoid synthesis pathways through AT1R on the submucosal plexus and surface epithelial cells in guinea pig distal colon.


1991 ◽  
Vol 260 (6) ◽  
pp. G835-G841 ◽  
Author(s):  
T. Frieling ◽  
H. J. Cooke ◽  
J. D. Wood

Intracellular recording methods were used in vitro to study the electrophysiological behavior of neurons in ganglia of the submucosal plexus in the distal colon of the guinea pig. The results revealed subpopulations of submucosal ganglion cells that corresponded to the AH/type 2, S/type 1, type 3, and type 4 subpopulations found elsewhere in the intestine. Electrical behavior of colonic submucosal neurons differed from the myenteric plexus of the colon, rectum, and stomach and the small intestinal submucosal plexus mainly in the relative proportions of the different subpopulations. Regional differences in this respect may be a reflection of functional specialization in the diverse regions of the alimentary canal.


1991 ◽  
Vol 261 (6) ◽  
pp. G1017-G1023 ◽  
Author(s):  
T. Frieling ◽  
H. J. Cooke ◽  
J. D. Wood

Intracellular microelectrodes were used to investigate the neuropharmacology of 5-hydroxytryptamine (5-HT) in the submucous plexus of the distal colon of the guinea pig. Three effects resulted from application of 5-HT to submucous neurons. Two of the effects were components of a biphasic depolarization mediated by receptors on the neuronal cell body. The third was suppression of acetylcholine release at nicotinic synapses on the cell bodies and was mediated by presynaptic 5-HT receptors. The initial component of the biphasic depolarization was a rapidly activating response characterized by increased ionic conductance and a tendency for rapid desensitization. Pharmacological analysis with selective agonists and antagonists suggested mediation of this response by the 5-HT3 receptor subtype. The second component of the depolarizing response was a slowly activating and long-lasting depolarization associated with decreased ionic conductance. Analysis of this response suggested it was mediated by the 5-HT1P receptor subtype. Identification of the presynaptic receptors for 5-HT was equivocal. These receptors did not behave like 5-HT3 or 5-HT1P receptor subtypes. The putative 5-HT4 agonist 5-methoxytryptamine was equipotent with 5-HT in producing presynaptic inhibition at the fast nicotinic synapses.


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