Co-axially stimulated ileum of the guinea pig

Shi G. Wong
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added without washing The tissue is washed several times and 0.35ml of 100g/ml of morphine is added. Naloxone is then added in concentrations of 0.5ml of 1g/ml, 0.1ml of 10g/ml, 0.35ml of 10g/ml, 0.1ml of 100g/ml and 0.35ml of 100g/ml. Results A rhythmic contraction of 10mm at 20V was selected. When 0.5ml of 0.1g/ml of acetylcholine is added, the contractions increases to 22mm. Referring to figure 3, at the first dose of morphine, a contraction of 18mm is achieved. 16mm of contraction is observed at the second dose. At the third dose, 14mm is achieved. At the fourth dose, 13mm is achieved. 12mm of contraction is achieved at the fifth dose and the same amount of contraction is obtained on the sixth and seventh dose. This shows the 12mm is the maximum contraction of the tissue. A contraction of 33mm is obtained when acetylcholine is added after cumulative dosing of morphine has been carried out. At figure 4, 0.35ml of 100g/ml of morphine is added and a contraction of 6mm is obtained. 10mm is contraction is obtained at the first dose of naloxone. At the second dose, 9mm is obtained. 8mm is obtained at the third dose. 21 mm is obtained at the fourth dose and 30mm is obtained at the last dose. Discussion The results shows that morphine reduces the contraction length. This is because morphine is a phenanthrene opioid receptor agonistits which binds to and activating the -opioid receptors in the central nervous system. It carries out its pharmacological effect at the central nervous system and gastrointestinal tract. Opioid receptor form proteins that couples to G-protein which closes the voltage gated Ca2+ channels on the presynaptic nerve terminals and reduces the release of transmitter. They also hyperpolarise and inhibits postsynaptic neurons by opening K+ channels. This causes stomach motility to decrease and increases the resting tone of the small intestine. Since the morphine is acting on the same receptor as acetylcholine, the action potantial of acetylcholine should be blocked but as acetylcholine is added, a large response was obtained. This is because morphine acts on the postsynaptic nicotinic receptor only. Acetylcholine can act on both postsynaptic and presynaptic nicotinic receptor.

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Introduction The effect of electrical stimulation, acetylcholine, morphine and naloxone was investigated upon isolated tissue of smooth muscle, the isolated ileum of the guinea pig with the cumulative dosing of tissues technique. Electrical stimulation is used to stimulate the parasympathetic neuron. Acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system while morphine is a highlypotent opiate analgesic drug. Naloxone is a drug used to counter the effects of opioid overdose. Acetylcholine acts as a neuromodulator. In the autonomic nervous system, acetylcholine is a major neurotransmiter. Acetylcholine also activatest he muscle in the peripheral nervous system. In the central nervous system, acetylcholine and other neurons tends to cause excitatory actions. Morphine is a prototypical opioid agonist. It produces analgesic actions by binding to specific G protein-coupled receptors, more specifically a -opioid receptors. Naloxone is a conpetitive antagonist drugs used to counter the effects of opioid overdose. It also binds to the same receptor as morphine in the central nervous system. Methods The Marriot bottle was filled half full with McEwens solution. The Grass recorder is set up following the instructions given out on a handout. The paper speed on the Grass recorder is set at 5mm/min. The preparation is set up with a 50ml isolated organ bath. The bath was equipped with two platinum wire electordes. A length of 3-4cm of ileum was taken and was carefully slid over the end of the glass J electrode. A thread was used to secure the ileum in place. A small piece of plastic tube is inserted to the top of the ileum and tied with a thread. The top thread is then attached to the forced tranducer. The resting tension is is adjusted to 05.g. The second electrode in the organ bath is adjusted such that it is parallel to the electrode inside the tissue. The Force Displacement Transducer have a setting of 20V and 0.1Hz with a pulse width of 1ms to stimulate the right nerve. After establishing the rhythmic contraction, 0.5ml of 0.1g/ml of acetylcholine is added with a 30 second contact time. The drug is then washed out. Morphine is added in concentrations of 0.5ml of 0.1g/ml, 0.1ml of 1g/ml, 0.35ml of 1g/ml, 0.1ml of 10g/ml, 0.35ml of 10g/ml, 0.1ml of 100g/ml and 0.35ml of 100g/ml with cumulative dosing. A 2 minute cycle is used. 0.5ml of 0.1g/ml of acetylcholine is

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Notes and references

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P.N. Bennett, M.J. Brown, Clinical Pharmacology, 9th Edition, Churchill Livingstone, 2003. 2 Rang, Dale and Ritter, Pharmacology, 4th Edition, Churchill Livingstone, 1999 Katzung, Basic and Clinical Pharmacology, 9th Edition, McGraw Hill, 2004 Walker and Whittlesea, Clinical Pharmacy and Therapeutics, 4th Edition, Churchill Livingstone, 2007

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As in the introduction, naloxone is a competitive antagonist which has a relatively high affinity for opioid receptors. They have lower affinity for other receptors but are also reverse agonists for and opioid receptors. This causes the ileum to contract more and return to its rhythmic contraction.

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EXPERIMENT REPORT CO-AXIALLY STIMULATED ILEUM OF THE GUINEA PIG NAME: SHI GUO WONG STUDENT ID: 059999354 DATE: 20 FEBRUARY 2008 TUTOR: DR. MUNBY

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