Contractile response

Figure 2. Effect of maitotoxin (MTX) on the log concentration—contractile response curve for Ca in the presence or absence of verapamil or MgCl2 in the rabbit aorta. Control (A), 10" g/mL MTX (o), 10" M verapamil plus 10 g/mL MTX ( ), and 10 mM MgCl2 plus 10" g/mL MTX ( ). The aorta was incubated in a Ca -free solution for 1 hr before the cumulative application of CaCL. Verapamil or MgCl2 and MTX were added 45 and 30 min before the application of CaCL, respectively. The maximum response to norepinephrine (3 x 10" M) is expressed as 100%. Vertical lines indicate the standard error of mean (n=7). (Reproduced with permission from Ref. 13. Copyright 1983 Press Syndicate of the University of Cambridge)...

Figure 3. The log concentration-contractile response curves for maitotoxin (MTX) on the developed tension of guinea pig left atria ( ) and rat ventricle strips (o). Vertical lines indicate the standard error of mean (n=6). (Reproduced with permission from Ref. 14. Copyright 1985 Macmillan)...

Figure 4. Effect of maitotoxin (MTX, 2-6 x 10 g/mL) on the contractile response of guinea pig left (a) and right (b) atria. MTX was administered at the arrow. Numbers above the tracing indicate the times after the application of MTX. The horizontal calibration indicates 4 min for the tracing recorded at a slower sweep speed and 4 sec for that recorded at faster speed. (Reproduced with permission from Ref. 20. Copyright 1987 Elsevier)...

Mechanical Response. PTX (5 x 10" to 3 x 10 M) caused a concentration-dependent contraction of the guinea pig vas deferens. The configuration of contractile response indicated the presence of two components, an initial rapid component followed by a second slow component. The first component of the response to PTX was abolished after treatment with Mg (10 mM), Ca -free medium, or ouabain (10 M), but remained almost unaffected by phentolamine (10 M), reserpine, 6-OHDA, atropine, or mecamylamine (10" M). The second component of the response to PTX was also completely inhibited after the incubation in the high or Ca -free medium. Phentolamine, reserpine, or 6-... 

The initial component of the PTX-induced contraction is selectively inhibited by ouabain, whereas the second component is rather potentiated by it (77). A similar inhibitory effect of ouabain on the contractile response to PTX is observed in the umbilical artery, which is devoid of adrenergic innervation 18). 

Nair, X. Contractile responses of guinea pig umbilical arteries to various hallucinogenic agents. Res Commun Chem Pathol Pharmacol 9 535-542, 1974. 

Macintosh, B. R., Barbee, R. W., and Stainsby, W. N., Contractile response to caffeine of rested and fatigued skeletal muscle, Medicine and Science in Sports and... 

Another possibility is that the antagonist interferes with other post-receptor events that contribute to the tissue response. For example, calcium channel blockers such as verapamil block the influx of calcium necessary for maintained smooth muscle contraction hence, they reduce the contractile response to acetylcholine. Some pharmacologists prefer to describe this as a variant of functional antagonism (see above). 

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 1.23 Effect of a 10-min exposure to two concentrations of a phenoxybenzamine-like compound, dibenamine (DB), on the contractile response of a strip of rabbit aorta to adrenaline (epinephrine). (From Furchgott, R. F., Adv. Drug Res., 3, 21-55, 1966.)... 

The family of concentration-response curves in Figure 1.23 shows the effect of an alkylating agent on the contractile response of rabbit aorta to adrenaline. Note the reduction in the maximal response, the departure from parallelism, and the fact that the exposure times as well as the concentrations of the antagonist have been given for each curve. 

Kitazawa T, Kobayashi S, Horiuti K, Somlyo AV, Somlyo AP 1989 Receptor coupled, permeabilized smooth muscle role of the phosphatidylinositol cascade, G proteins and modulation of the contractile response to Ca2+. J Biol Chem 264 5339-5342 Lopez-Lopez JR, Shacklock PS, Balke CW, Wier WG 1995 Local calcium transients triggered by single L-type calcium channel currents in cardiac cells. Science 268 1042-1045 Marks AR, Fleischer S, Tempst P 1990 Surface topography analysis of the ryanodine receptor/ junctional channel complex based on proteolysis sensitivity mapping. J Biol Chem 265 13143-13149... 

Kotlikojf These animals have an altered contractile response to agonists in vitro. This is about as much as we can say at the moment. We do see a phenotype in terms of their contractile properties. In the RyR2 knockouts we would expect to have a loss of stretch-induced Ca2+ release and CICR in smooth muscle. If you have normal pressurized vasomotor responses in those animals, I think this would suggest that the phenomenon that we have described is not essential for myogenic tone. 

Rohrmann D, Zderic SA, Wein AJ, Levin RM 1996 Effect of thapsigargin on the contractile response of the normal and obstructed rabbit urinary bladder. Pharmacology 52 119-124... 

Sawyer, G. W. and Ehlert, F. J. (1999) Muscarinic M3 receptor inactivation reveals a pertussis toxin-sensitive contractile response in the guinea pig colon evidence for M2/M3 receptor interactions../. Pharmacol. Exp. Ther. 289,464-476. 

Figure 7.1. The effect of ondansetron on contractile responses to 2-methyl-5-HT in the guinea-pig isolated longitudinal muscle myenteric plexus preparation. Symbols indicate control responses (9) or in the presence of ondansetron at 1 x 10- M (O) or 1 x 10 M ( ). Results + S.E.M. of at least four separate observations. Experiments were performed as described by Butler...

Ohizumi, Y. and Yasumoto, T., Contractile response of the rabbit aorta to maitotoxin, the most potent marine toxin, J. Physiol., 337, 711, 1983. 

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