Guinea ileum

Long-lasting vasoconstriction is produced by the ETs in almost all arteries and veins and several studies have shown that ET-1 causes a reduction in renal blood flow and urinary sodium excretion. ET-1 has been reported to be a potent mitogen in fibroblasts and aortic smooth muscle cells and to cause contraction of rat stomach strips, rat colon and guinea pig ileum. In the central nervous system, ETs have been shown to modulate neurotransmitter release. 

FIGURE 2.19 Potentiation and modulation of response through control of cellular processes, (a) Potentiation of inotropic response to isoproterenol in guinea pig papillary muscle by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX). Ordinates percent of maximal response to isoproterenol. Abscissa percent receptor occupancy by isoproterenol (log scale). Responses shown in absence (open circles) and presence (filled circles) of IBMX. Data redrawn from [7], (b) Effect of reduction in calcium ion concentration on carbachol contraction of guinea pig ileum. Responses in the presence of 2.5 mM (filled circles) and l.5mM (open circles) calcium ion in physiological media bathing the tissue. Data redrawn from [8],... 

Kenakin, T. P., and Cook, D. A. (1980). N,N-Diethyl-2-(l-pyridyl)ethylamine, a partial agonist for the histamine receptor in guinea pig ileum. Can. J. Physiol. Pharmacol. 58 1307-1310. 

Supra-additivity This is a special case of cooperation where the blockade of a single receptor is not sufficient to reduce the overall response. Capsaicin-induced nonadrenergic, noncholinergic contraction in the guinea pig ileum or common bile duct can be inhibited only when at least two different TK receptors are blocked (e.g., NKX + NK2, NKX + NK3, NK2 + NK3)... 

In squid giant axons, PbTx causes a depolarization of the plasma membrane, repetitive discharges followed by depression of action potentials, and a complete blockade of excitability. This action is antagonized by TTX (83,84). PbTx depolarizes nerve terminals and induces neurotransmitter release (85,86) it depolarizes skeletal muscle cells (87) and increases the frequency of action potentials in crayfish nerve cord (88). PbTx also produces a contraction of the guinea pig ileum (89). All these effects are prevented by TTX. 

Sea urchin toxins extracted from spines or pedicellariae have a variety of pharmacological actions, including electrophysiological ones (75). Dialyzable toxins from Diadema caused a dose-dependent increase in the miniature end-plate potential frequency of frog sartorius muscle without influencing membrane potential (76). A toxin from the sea urchin Toxopneustes pUeolus causes a dose-dependent release of histamine (67). Toxic proteins from the same species also cause smooth muscle contracture in guinea pig ileum and uterus, and are cardiotoxic (77). 

Lis-BALCHIN M, HART s, SIMPSON E (2001) Buchu (Aguthosmu betuUna and. crenulata, Rutaceae) essential oils their pharmacological action on guinea-pig ileum and antimicrobial activity on microorganisms. J Pharm Pharmacol. S3 579-82. 

The collaboration between several academic laboratories has shown that the imidazole moiety on some of the earlier H3 antagonists can be replaced with a piperidine. For example, the ciproxifan analogue (16) has a pK of 8.4 in rat cerebral cortex [80]. This compound showed in vivo efficacy after p.o. administration to a mouse. Other piperidines studied by these researchers include (17) (H3 p 2 = 7.21 in guinea-pig ileum) [81] and (18) (human K[ — 2.8 nM, p 2 = 7.42 in guinea-pig ileum) [82]. The authors have also found that benzyl ethers such as (19) are somewhat weaker H3 antagonists (p 2 = 6.3 in guinea-pig ileum) [83]. 

Delta receptors are relatively selective for two related penta-peptides, methionine enkephalin and leucine enkephalin (met- and leu-enkephalin), which were isolated from porcine brain (Hughes 1975). Both met- and leu-enkephalin inhibit electrically induced contractions of guinea pig ileum, an effect that mimics those effects seen with opioid drugs, and is naloxone reversible. The enkephalins are processed posttranslational ly from proenkephalin, and secreted from central and peripheral neurons and endocrine cells in the adrenal medulla. 

In addition, anandamide was found to parallel classical cannabinoid pharmacology in a series of nonbehavioral experimental systems. In isolated MVD, (Pertwee, 1992) and guinea pig ileum, it inhibited electrically evoked twitch responses (Pertwee, 1995). Moreover, anandamide was shown to decrease intraocular pressure in rabbits (Pate, 1995), to reduce sperm-fertilizing capacity in sea urchins by inhibition of the acrosome reaction (Schuel, 1994), and to produce hypotension in rats (Varga, 1995). 

A Schild plot (based on the results of a student class experiment on the effect of atropine on the contractile response of guinea-pig ileum to acetylcholine) is shown in Figure 1.17. Note that the line is straight, and its slope is close to unity, as Eq. (1.51) predicts. 

FIGURE 1.17 Schild plot for the action of atropine in antagonizing the action of acetylcholine on guinea-pig ileum. Each point gives the mean the standard error of the mean of the number of observations shown. 

Comparison of the Ability of Burimamide to Block the Actions of Histamine on Guinea-Pig (G.-P.) Ileum and Atrium and on Rat Uterus... 

Many measurements in pharmacology rely on a chain of events following receptor activation to produce a measurable response — for example, contraction of the smooth muscle of a piece of guinea-pig ileum in response to muscarinic receptor activation by acetylcholine. This means that the relationship between receptor occupancy and response is likely to be complex, and mechanisms of drug action in such systems are often difficult to define. 

Cooke, H.J. (1984) Influence of enteric cholinergic neurons on mucosal transport in guinea pig ileum. American Journal of Physiology 246, G263—G267. 

A guinea pig ileum bioassay was used to detect and aid in the isolation of a smooth-muscle-contracting substance from the Japanese gorgonian coral Euplexaura erecta [108]. This process led to the isolation of prostaglandin F2a (17) from the MeOH extract of the coral. Its identification was based on comparison with authentic PGF2a and its methyl ester by TLC, and comparison with authentic methyl PGF2a trimethylsilyl ether by mass spectrometry. Because of the nature of the techniques employed, some aspects of the stereochemistry in this isolate of PGF2a remain uncertain. 

Gordienko DV, Bolton TB, Cannell MB 1998 Variability in spontaneous subcellular calcium release in guinea-pig ileum smooth muscle cells. J Physiol 507 707—720... 

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