W1363 Real Time Detection and Function of Melatonin Release from the Mucosa of Guinea Pig Ileum

Venomous mammals are rare, and only a few species in the orders Insectivora and Monotremata produce toxic venom. Among them, the duckbill platypus (Ornithorhynchus anatinus) is one of the two venomous Australian mammals. The adult male platypus carries a spur on each hind leg, which it uses to inject competitors with poison. However, the structure and function of the poison’s active compounds are still imcompletely characterized. We found that crude platypus venom produced potent Ca2+influx in human neuroblastoma IMR-32 cells. Guided by this assay, we identified 11 unique peptides, including peptide H–His–Asp–His–Pro–Asn–Pro–Arg–OH, which coincided with the N-terminal domain residues ofOrnithorhynchusvenom C-type natriuretic peptide (OvCNP). This heptapeptide induced a significant increase in [Ca2+]iin IMR-32 cells at 75 μM; had relatively specific affinities for glutamate, histamine, and GABAAreceptors; and facilitated neurogenic twitching in guinea pig ileum specimens at 30 μM. We also established that its proteinous venom fraction strongly hydrolyzed Pro–Phe–Arg–MCA and cleaved a human low-molecular-weight kininogen (LK), similar to porcine pancreas kallikrein. These results strongly indicated that platypus venom contains tissue kallikrein-like protease(s), and its proteolytic activity might synergistically contribute to toxicity through the specific cleavage of other venom constituents.

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Cannabinoid CB1 receptor distribution and function in neurally mediated chloride secretion in the guinea pig ileum

Gastroenterology ◽

10.1016/s0016-5085(03)81726-2 ◽

2003 ◽

Vol 124 (4) ◽

pp. A342 ◽

Cited By ~ 2

Author(s):

Wallace K. Macnaughton ◽

Kelly Cushing ◽

Marja D. Van Sickle ◽

Catherine M. Keenan ◽

Kenneth Mackie ◽

...

Keyword(s):

Guinea Pig ◽

Chloride Secretion ◽

Cb1 Receptor ◽

Cannabinoid Cb1 Receptor ◽

Guinea Pig Ileum ◽

And Function ◽

Receptor Distribution

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Real-time measurement of serotonin release and motility in guinea pig ileum

The Journal of Physiology ◽

10.1113/jphysiol.2006.117804 ◽

2006 ◽

Vol 577 (2) ◽

pp. 689-704 ◽

Cited By ~ 80

Author(s):

Paul P. Bertrand

Keyword(s):

Guinea Pig ◽

Real Time ◽

Time Measurement ◽

Serotonin Release ◽

Guinea Pig Ileum ◽

Real Time Measurement

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Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00482.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. G863-G871 ◽

Cited By ~ 30

Author(s):

Wallace K. MacNaughton ◽

Marja D. Van Sickle ◽

Catherine M. Keenan ◽

Kelly Cushing ◽

Ken Mackie ◽

...

Keyword(s):

Guinea Pig ◽

Ion Transport ◽

Transient Receptor Potential ◽

Short Circuit ◽

Inhibitory Effect ◽

Transient Receptor Potential Vanilloid ◽

Submucosal Plexus ◽

Guinea Pig Ileum ◽

And Function ◽

Secretomotor Neurons

We investigated the distribution and function of cannabinoid (CB)1receptors in the submucosal plexus of the guinea pig ileum. CB1receptors were found on both types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively. CB1receptors colocalized with transient receptor potential vanilloid-1 receptors on paravascular nerves and fibers in the submucosal plexus. In the submucosal ganglia, these nerves were preferentially localized at the periphery of the ganglia. In denervated ileal segments, CB1receptor immunoreactivity in submucosal neurons was not modified, but paravascular and intraganglionic fiber staining was absent. Short-circuit current ( Isc) was measured as an indicator of net electrogenic ion transport in Ussing chambers. In the ion-transport studies, Iscresponses to capsaicin, which activates extrinsic primary afferents, and to electrical field stimulation (EFS) were reduced by pretreatment with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were unaffected by VIP receptor desensitization, hexamethonium, α-amino-3-hydroxy-5-methlisoxazole-4-proprionic acid, or N-methyl-d-aspartate glutamate receptor antagonists. The responses to capsaicin and EFS were reduced by 47 ± 12 and 30 ± 14%, respectively, by the CB1receptor agonist WIN 55,212–2. This inhibitory effect was blocked by the CB1receptor antagonist, SR 141716A. Iscresponses to forskolin or carbachol, which act directly on the epithelium, were not affected by WIN 55,212–2. The inhibitory effect of WIN 55,212–2 on EFS-evoked secretion was not observed in extrinsically denervated segments of ileum. Taken together, these data show cannabinoids act at CB1receptors on extrinsic primary afferent nerves, inhibiting the release of transmitters that act on cholinergic secretomotor pathways.

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