Histamine action on guinea pig ileal mucosa

1984 ◽  
Vol 246 (4) ◽  
pp. G372-G377 ◽  
Author(s):  
H. J. Cooke ◽  
P. R. Nemeth ◽  
J. D. Wood
Keyword(s):  
Receptor Agonist ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Chloride Secretion ◽  
Evoked Response ◽  
Field Stimulation ◽  
H1 Receptor ◽  
Electrical Field ◽  
Mucosal Response

Nerve-mediated and direct actions of histamine on mucosal transport function in the guinea pig ileum were investigated. Addition of histamine to the serosal side of flat sheet preparations in Ussing chambers evoked a transient increase in base-line short-circuit current that was due primarily to an increase in active chloride secretion. The mucosal response to histamine was mimicked by the H1-receptor agonist 2-methylhistamine, but not by the H2-receptor agonist dimaprit. The histamine-evoked response was prevented by the H1-receptor blocker pyrilamine, but not by the H2-receptor antagonist cimetidine. Thirty percent of the mucosal response to histamine was inhibited by tetrodotoxin. Intracellular electrical recording showed that histamine activated AH/type 2 myenteric neurons, and this response was abolished in the presence of pyrilamine. Local anesthetic action of pyrilamine was ruled out by direct electrical recording from myenteric neurons in the presence and absence of pyrilamine. Electrical field stimulation evoked a biphasic increase in short-circuit current. Histamine and 2-methylhistamine did not alter the sustained phase of the short-circuit current response to electrical field stimulation, although pyrilamine reduced the electrically evoked response by 22%. Muscarinic blockade with atropine reduced the stimulus-evoked response by 55%. When muscarinic receptors were blocked and electrical field stimulation applied, histamine increased the stimulus-evoked mucosal response by 22.3%. These results suggest that histamine increases short-circuit current and chloride secretion by acting at H1-receptor sites on both the enteric innervation of the mucosa and on the enterocytes.

Chymotrypsin, ileal chloride transport, and neurotransmitters

1984 ◽  
Vol 247 (3) ◽  
pp. G253-G260 ◽  
Author(s):  
K. A. Hubel
Keyword(s):  
Cell Function ◽  
Chloride Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Chloride Secretion ◽  
Target Cells ◽  
Flux Chamber ◽  
Rabbit Ileum ◽  
Electrical Field

Electrical field stimulation (EFS) depolarizes nerves and causes chloride secretion by mucosa of rabbit ileum mounted in a flux chamber. To test the hypothesis that the transmitter is a peptide, we determined whether the EFS response was prevented by the endopeptidase chymotrypsin (CT). Serosal, but not mucosal, addition of CT (200 micrograms/ml) reduced the short-circuit current (Isc) response to EFS by 90% or more. CT also reduced Cl absorption by decreasing the mucosal-to-serosal flux, but it did not affect net Na absorption. CT prevented the response to vasoactive intestinal polypeptides, but the response returned when CT activity was eliminated. The response to EFS did not return, however, implying that CT damaged cells that released transmitter or epithelial target cells. CT reduced the Isc response to serotonin by 69% and to A23187 by 10% and did not affect the theophylline response. We conclude that 1) the effects of CT on cell function limit its usefulness in identifying peptide neurotransmitters in epithelium, 2) CT irreversibly inhibits ion transport responses to EFS and to serotonin, and 3) CT reduces absorption of Cl probably by affecting a calcium pathway that modifies Cl transport.

Noradrenergic influence on epithelial responses of rabbit ileum to secretagogues

1989 ◽  
Vol 256 (5) ◽  
pp. G919-G924 ◽  
Author(s):  
K. A. Hubel ◽  
K. S. Renquist ◽  
G. Varley
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Rabbit Ileum ◽  
Electrical Field ◽  
Physiological Importance ◽  
Intrinsic Nerves ◽  
Pm 10

Norepinephrine is one of three neurotransmitters that may act directly on enterocytes to enhance absorption; its interaction with secretagogues is of physiological importance. We have studied the influence of norepinephrine on the short-circuit current (Isc) responses to acetylcholine (ACh; 10 microM), vasoactive intestinal polypeptide (VIP; 100 pM-10 nM), peptide histidine isoleucine (PHI; 100 pM-10 nM), histamine (0.1 mM), and to electrical field stimulation (EFS) of rabbit ileum mounted in flux chambers. Tetrodotoxin reduced the response to norepinephrine (10 microM) by 40% and to histamine by 32% but did not affect responses to VIP or PHI. Norepinephrine decreased the ACh response (EC50, 70 nM) and reduced the responses to PHI (less than or equal to 87%), to EFS (less than or equal to 75%), and to histamine (less than or equal to 42%). Norepinephrine decreased the response to VIP (500 pM) but not to higher or lower VIP concentrations. It enhanced the response to VIP (10 nM) and to theophylline (5 mM). We conclude that 1) norepinephrine increases absorption by acting on nerves and enterocytes; 2) the failure of norepinephrine to reduce the Isc response to VIP when the VIP-induced increment in Isc is comparable to that caused by EFS is evidence that VIP does not mediate the EFS response; 3) PHI might mediate the EFS response; and 4) VIP, PHI, and histamine affect enterocytes directly; histamine also affects intrinsic nerves.

5-HT activates nitric oxide-generating neurons to stimulate chloride secretion in guinea pig distal colon

1998 ◽  
Vol 275 (4) ◽  
pp. G829-G834 ◽  
Author(s):  
Atsukazu Kuwahara ◽  
Hirofumi Kuramoto ◽  
Makoto Kadowaki
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Evoked Response ◽  
Evoked Responses ◽  
No Donor ◽  
Simultaneous Application

The participation of nitric oxide (NO) in serotonin (5-hydroxytryptamine; 5-HT)-evoked chloride secretion in guinea pig distal colon was examined. Submucosal/mucosal segments were mounted in Ussing flux chambers, and an increase in short-circuit current ( I sc) was used as an index of secretion. Addition of 5-HT to the serosal side produced a concentration-dependent (10−7–10−5M) increase in I sc caused by chloride secretion. N G-nitro-l-arginine (l-NNA) significantly reduced the 5-HT-evoked early (P-1) and late (P-2) responses to 61.1 and 70.6% of control, respectively. Neurally evoked response was also inhibited by l-NNA. The NO donor sodium nitroprusside (SNP, 10−4 M) increased basal I sc mainly because of chloride secretion. The SNP-evoked response was significantly reduced by tetrodotoxin but was unchanged by atropine or indomethacin. These results suggest that the 5-HT-evoked increase in I sc is associated with an NO-generating mechanism. Atropine significantly reduced the 5-HT (10−5 M)-evoked P-1 and P-2 responses to 71.8 and 19.7% of control, respectively. Simultaneous application of atropine andl-NNA further decreased the 5-HT-evoked responses more than either drug alone; application ofl-NNA and atropine decreased the 5-HT-evoked P-1 and P-2 responses to 68.5 and 39.2% of atropine-treated tissues, respectively. These results suggest that noncholinergic components of P-1 and P-2 responses are 71.8 and 19.7% of control, respectively, and that NO components of P-1 and P-2 responses are 32 and 61%, respectively, of the noncholinergic component of the 5-HT-evoked responses. The results provide evidence that NO may participate as a noncholinergic mediator of 5-HT-evoked chloride secretion in guinea pig distal colon.

Effects of tetrodotoxin on chloride secretion in rabbit distal colon: tissue and cellular studies

1990 ◽  
Vol 258 (2) ◽  
pp. G223-G230 ◽  
Author(s):  
B. Biagi ◽  
Y. Z. Wang ◽  
H. J. Cooke
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Resting Potential ◽  
Colon Tissue ◽  
Colonic Crypts ◽  
Electrophysiological Studies ◽  
Release Of Acetylcholine

The effects of tetrodotoxin (TTX) were examined in muscle-stripped segments of rabbit distal colon and in cells of isolated colonic crypts. Electrical field stimulation (EFS) of the submucosa/mucosa evoked an increase in short-circuit current (ISC) that was due to an increase in chloride secretion. The EFS-evoked response was reduced 81% by 10(-7) M TTX and 30% by 5 X 10(-6) M atropine. Vasoactive intestinal peptide (VIP), carbachol, aminophylline, and 1,1-dimethyl-4-phenylpiperazinium increased ISC. Bumeta nide reduced the responses to neural stimulation, aminophylline, and VIP. To determine whether TTX had direct effects on crypt epithelial cells, crypts were isolated and cells were impaled with microelectrodes. Mean resting potential (Vbl) was -67 +/- 1.1 mV (n = 63). VIP and aminophylline depolarized Vbl by 34 +/- 4.6 (n = 13) and 34 +/- 3.5 mV (n = 18), respectively. TTX had no significant effect on resting Vbl or on the responses to VIP or aminophylline. We conclude that stimulation of submucosal neurons in the rabbit distal colon evokes a TTX- and bumetanide-sensitive increase in net chloride secretion that is dependent on the release of acetylcholine and other secretory neurotransmitters. Electrophysiological studies rule out a direct effect of TTX on colonic crypt cells.

Dual purinergic synaptic transmission in the human enteric nervous system

2008 ◽  
Vol 294 (2) ◽  
pp. G554-G566 ◽  
Author(s):  
J. E. Wunderlich ◽  
B. J. Needleman ◽  
Z. Chen ◽  
J. G. Yu ◽  
Y. Wang ◽  
...  
Keyword(s):  
Nervous System ◽  
Synaptic Transmission ◽  
Enteric Nervous System ◽  
Laser Scanning ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Chloride Secretion ◽  
Suitable Model ◽  
Frequency Dependent

Based on findings in rodents, we sought to test the hypothesis that purinergic modulation of synaptic transmission occurs in the human intestine. Time series analysis of intraneuronal free Ca2+ levels in submucosal plexus (SMP) from Roux-en-Y specimens was done using Zeiss LSM laser-scanning confocal fluo-4 AM Ca2+ imaging. A 3-s fiber tract stimulation (FTS) was used to elicit a synaptic Ca2+ response. Short-circuit current ( Isc = chloride secretion) was recorded in mucosa-SMP in flux chambers. A distension reflex or electrical field stimulation was used to study Isc responses. Ca2+ imaging was done in 1,222 neurons responding to high-K+ depolarization from 61 surgical cases. FTS evoked synaptic Ca2+ responses in 62% of recorded neurons. FTS caused frequency-dependent Ca2+ responses (0.1–100 Hz). FTS Ca2+ responses were inhibited by Ω-conotoxin (70%), hexamethonium (50%), TTX, high Mg2+/low Ca2+ (≤100%), or capsaicin (25%). A P2Y1 receptor (P2Y1R) antagonist, MRS-2179 or PLC inhibitor U-73122, blocked FTS responses (75–90%). P2Y1R-immunoreactivity occurred in 39% of vasoactive intestinal peptide-positive neurons. The selective adenosine A3 receptor (AdoA3R) agonist 2-chloro- N6-(3-iodobenzyl)adenosine-5′- N-methylcarboxamide (2-Cl-IBMECA) caused concentration- and frequency-dependent inhibition of FTS Ca2+ responses (IC50 = 8.5 × 10−8 M). The AdoA3R antagonist MRS-1220 augmented such Ca2+ responses; 2-Cl-IBMECA competed with MRS-1220. Knockdown of AdoA1R with 8-cyclopentyl-3- N-(3-{[3-(4-fluorosulphonyl)benzoyl]-oxy}-propyl)-1- N-propyl-xanthine did not prevent 2-Cl-IBMECA effects. MRS-1220 caused 31% augmentation of TTX-sensitive distension Isc responses. The SMP from Roux-en-Y patients is a suitable model to study synaptic transmission in human enteric nervous system (huENS). The P2Y1/Gαq/PLC/inositol 1,3,5-trisphosphate/Ca2+ signaling pathway, N-type Ca2+ channels, nicotinic receptors, and extrinsic nerves contribute to neurotransmission in huENS. Inhibitory AdoA3R inhibit nucleotide or cholinergic transmission in the huENS.

ICS 205-930 reduces 5-methoxytryptamine-induced short-circuit current in stripped pig jejunum

1994 ◽  
Vol 72 (3) ◽  
pp. 227-232 ◽  
Author(s):  
Mark Berner Hansen
Keyword(s):  
Receptor Agonist ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Intestinal Secretion ◽  
Chloride Secretion ◽  
Receptor Subtype ◽  
Ics 205 930 ◽  
Peak Increase ◽  
Pig Jejunum

The effect of ICS 205-930 on serotonin (5-hydroxytryptamine, 5-HT) and 5-methoxytryptamine (5-MeOT) induced short-circuit current (SCC) was studied in muscle-stripped pig jejunum in vitro. The selective 5-HT4 receptor agonist 5-MeOT and 5-HT both induced a concentration-dependent increase in SCC. The maximal efficacy of 5-HT was twice that of 5-MeOT. ICS 205-930 (Tropisetron) induced a small increase in SCC. Furthermore, ICS 205-930 reduced the 5-MeOT but not the 5-HT induced increase in SCC, except at the 100 μM ICS 205-930 concentration. Pretreatment with bumetanide reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 64, 75, and 58%, respectively. Pretreatment with atropine reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 38, 75, and 58%, respectively. Pretreatment with hexamethonium reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 33, 50, and 36%, respectively. Pretreatment with tetrodotoxin reduced the peak increase in SCC elicited by 5-MeOT and ICS 205-930 by 41 and 50%, respectively. This study demonstrates involvement of a ICS 205-930, hexamethonium, atropine, bumetanide, and tetrodotoxin sensitive receptor in 5-MeOT induced SCC in muscle-stripped pig jejunum in vitro. These data suggest involvement of a neuronal 5-HT4 receptor subtype and acetylcholine in 5-HT elicited SCC and chloride secretion in the pig jejunum.Key words: intestinal secretion, 5-hydroxytryptamine, 5-methoxytryptamine, jejunum, antagonists, pig, Tropisetron, ICS 205-930.

Acetylcholine release from colonic submucous neurons associated with chloride secretion in the guinea pig

1992 ◽  
Vol 262 (1) ◽  
pp. G131-G136 ◽  
Author(s):  
N. H. Javed ◽  
H. J. Cooke
Keyword(s):  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Ach Release ◽  
Response Characteristics ◽  
Flux Chambers

Electrical field stimulation of submucous neurons in the guinea pig distal colon evokes an increase in chloride secretion sensitive to cholinergic blockade. This study was undertaken in the guinea pig to determine the feasibility of measuring acetylcholine (ACh) release simultaneously with ion transport in sheets of colonic submucosa/mucosa set up in flux chambers modified for perfusion of the submucosal surface. Release of [3H]ACh was determined in the absence of cholinesterase inhibitors as the stimulus-evoked outflow of 3H from preparations preloaded with [3H]choline. [3H]ACh released in response to electrical stimulation correlated with short-circuit current at frequencies from 0.5 to 10 Hz. At 5 and 10 Hz, the stimulus-evoked release of [3H]ACh decreased during subsequent stimulation periods. The stimulus-evoked increase in [3H]ACh was attenuated by tetrodotoxin. [3H]ACh release evoked at stimulus frequencies of 0.5-10 Hz was not altered by atropine despite a reduction in short-circuit current. This study illustrates the feasibility of measuring ACh release simultaneously with ion transport in flux chambers. The results provide new information on the response characteristics of colonic submucous neurons and provide direct evidence for regulation of chloride secretion by ACh.

Neuromodulation of intestinal transport in the suckling mouse

1989 ◽  
Vol 256 (2) ◽  
pp. R481-R486 ◽  
Author(s):  
H. V. Carey ◽  
H. J. Cooke
Keyword(s):  
Short Circuit ◽  
Sugar Transport ◽  
Intestinal Transport ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Chloride Secretion ◽  
Intestinal Wall ◽  
Neural Stimulation ◽  
Secretory Response ◽  
Suckling Mouse

The influence of enteric nerves on intestinal ion and sugar transport was investigated in 3- to 4-wk-old suckling mice. Whole thickness segments of jejunum were mounted as flat sheets in flux chambers equipped to electrically stimulate nerves in the intestinal wall. Tetrodotoxin significantly reduced basal short-circuit current in a subset of tissues containing 3-O-methylglucose in the mucosal bath. Electrical field stimulation of intrinsic nerves evoked an increase in short-circuit current of 86 +/- 15 microA/cm2 that was due to an increase in active chloride secretion with no significant change in the net movement of other ions. The secretory response to neural stimulation was abolished by tetrodotoxin and reduced by the muscarinic antagonist, atropine. Mucosal-to-serosal fluxes of 3-O-methylglucose were not altered by the cholinergic agonist carbachol. These results show that ion transport in the suckling mouse jejunum is regulated by the enteric nervous system. Neural stimulation evokes a chloride secretory response that is mediated by acetylcholine and other noncholinergic transmitters. Sugar transport in the murine small intestine does not appear to be influenced by muscarinic cholinergic agonists.

Neural 5-hydroxytryptamine receptors regulate chloride secretion in guinea pig distal colon

1991 ◽  
Vol 261 (5) ◽  
pp. G833-G840 ◽  
Author(s):  
H. J. Cooke ◽  
Y. Z. Wang ◽  
T. Frieling ◽  
J. D. Wood
Keyword(s):  
Guinea Pig ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Cl Secretion ◽  
Release Of Acetylcholine ◽  
Ics 205 930 ◽  
Stimulation Of

The effects of 5-hydroxytryptamine (5-HT) on epithelial short-circuit current (Isc) were determined and related to the 5-HT effects on electrical and synaptic behavior of neurons in the submucosal plexus of the guinea pig colon. 5-HT evoked a biphasic increase in Isc that was reduced by bumetanide, Cl(-)-free solutions, atropine, and mecamylamine and abolished by tetrodotoxin. The 5-HT response was mimicked by 2-methyl-5-HT, but not by 5-hydroxyindalpine, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, and 5-methoxytryptamine (5-MeOT). ICS 205-930 suppressed the 5-HT response. Electrical field stimulation of submucosal neurons evoked an increase in Isc indicative of Cl- secretion that was reduced by 5-MeOT and enhanced by 2-methyl-5-HT. Application of 5-HT to submucosal neurons by micropressure ejection resulted in membrane depolarization, augmented excitability, and repetitive spike discharge. The depolarization was biphasic, consisting of rapidly and slowly activating components. The rapidly activating component was suppressed by ICS 205-930. Fast excitatory postsynaptic potentials evoked by electrical stimulation of interganglionic connectives were suppressed by 5-HT and 5-MeOT. These results suggest that 5-HT activates 5-HT3 receptors, which mediate fast excitatory responses in submucosal neurons, leading to release of acetylcholine at nicotinic and muscarinic synapses and stimulation of Cl- secretion. Presynaptic inhibition suppresses acetylcholine release and results in attenuation of neurally evoked Cl- secretion.

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