Guinea pig atria

The smallest sequence possessing most of the neurotensin spectmm of activities and its high potency is the hexapeptide C-terminus (1). [D-Trp ]-Neurotensin acts like a neurotensin antagonist in perfused heart preparations, but acts like a full agonist in guinea pig atria and rat stomach strips (122). 

FIGURE 2.18 Inotropic and lusitropic responses of guinea pig left atria to (3-adrenoceptor stimulation. Panels A to C isometric tension waveforms of cardiac contraction (ordinates are mg tension abscissae are msec), (a) Effect of 0.3 nM isoproterenol on the waveform. The wave is shortened due to an increase in the rate of diastolic relaxation, whereas no inotropic response (change in peak tension) is observed at this concentration, (b) A further shortening of waveform duration (lusitropic response) is observed with 3 nM isoproterenol. This is concomitant with positive inotropic response (increase maximal tension), (c) This trend continues with 100 nM isoproterenol, (d) Dose-response curves for ino tropy (filled circles) and lusitropy (open circles) in guinea pig atria for isoproterenol, (e) Dose-response curves for inotropy (filled circles) and lusitropy (open circles) in guinea pig atria for the P-adrenoceptor partial agonist prenalterol. Data redrawn from [6]. 

FIGURE 2.21 Effects of desensitization on inotropic responses of guinea pig atria to isoproterenol (panel a) and prenalterol (panel b). Ordinates response as a percent of the maximal reaponse to isoproterenol. Abscissae logarithms of molar concentrations of agonist (log scale). Responses shown after peak response attained (within 5 minutes, filled circles) and after 90 minutes of incubation with the agonist (open triangles). Data redrawn from [6]. 

Comparison of the Antagonism by Burimamide of the Actions of Histamine and Two Related Agonists on Guinea-Pig Atria... 

Table 3 shows pA values for practolol and propranolol against isoprenaline induced tachycardia in the guinea pig atria, relaxation of the tracheal chain, and adenylate cyclase activity of purified membrane fragments prepared from guinea pig heart and lung. While practolol is clearly cardioselective in the tissue preparations it becomes non-selective on the membrane fragments. It is conceivable that in the purification of the membranes the integrity of the micro-environment which controls access to the receptors in the different tissues, is destroyed. 

About scaritoxin, the following results were reported. This toxin was found to depress the oxidative metabolic process in the rat brain (20) and to have a depolarizing action on excitable membranes (38). In the guinea-pig atria, scaritoxin caused a marked potentiation of the acetylcholine negative inotropic and chronotropic effects (39). In rat atria, we observed biphasic inotropic and chronotropic effects similar to those of ciguatoxin. Negative inotropic and chronotropic effects were antagonized by atropine. 

Maitotoxin effects were investigated also by in )iXA,0 experiments. Miyahara oX dt (31) reported a biphasic response in the guinea-pig atria, an initial positive response followed by a progressive decrease of both the rate and the force of contractions. 

Physiological studies show that monensin is a sodium ionophore (15), that induces inotropic effect on guinea pig atria (17). The polyether toxins including ciguatoxin, okadaic acid, and the recently characterized brevetoxin (5, 16) also induce inotropic effect on guinea pig atrial tissue in vitro (17). Additionally, partially purified CTX has been implicated in the depolarization of nerve cells in vitro, which can be reversed by high concentrations of Ca tetrodotoxin and saxitoxin (18). 

Classically, these receptors have also been divided into three groups. The first of these, the Hj receptors, were described by Schild in 1966. The Hj receptors were discovered in 1972 by Black et al. The Hj receptor subtype was described by Arrang in 1983. The Hj receptor is found in the smooth muscle of the intestines, bronchi, and blood vessels and is blocked by the classical antihistamines. The Hj receptor, present in gastric parietal cells, in guinea pig atria, and in the uterus, does not react to H, blockers but only to specific Hj antagonists. Hj receptors also appear to be involved in the immunoregulatory system and may be present in T lymphocytes, basophil cells, and mast cells. Hj receptors are found predominantly in brain but are also localized in stomach, lung, and cardiac tissue. 

FIGURE 6. Affinities (Jvl2 values) of the (/ ) and (.V) enantiomers of 11 and 13 for muscarinic Ml (rabbit vas deferens), M2 (guinea-pig atria) and M3 receptors (guinea-pig ileum)... 

Gan XT, Rajapurohitam V, Haist JV, Chidiac P, Cook MA, Karmazyn M (2005) Inhibition of phenylephrine-induced cardiomyocyte hypertrophy by activation of multiple adenosine receptor subtypes. J Pharmacol Exp Ther 312(1) 27—34 Gardner NM, Yates L, Broadley KJ (2004) Effects of endogenous adenosine and adenosine receptor agonists on hypoxia-induced myocardial stunning in guinea-pig atria and papillary muscles. J Cardiovasc Pharmacol 43(3) 358-368... 

Noncompetitive antagonist of histamine, isoproterenol, and Ca2+ in isolated guinea pig atria decreased contractile force and attenuated adrenalin response 610... 

Inhibition of neurotransmitter release mediated by Ai adenosine receptors is a widespread phenomenon. As mentioned in Section 1, it was first described for cholinergic neurons. But presynaptic Ai receptors also inhibit the release of several other neurotransmitters both in CNS and PNS. Table 2 summarizes early relevant studies. As to postganglionic parasympathetic neurons, there is only one study to our knowledge. In that study, carried out in guinea pig atria, no A] receptor-mediated modulation of acetylcholine release was found (Nakatsuka et al. 1995). 

The effect of the aminoglycosides dibekacin, sisomicin, and gentamicin on Ca2+ bound to the outer surface of the cardiac plasmalemma on contraction in guinea-pig atria has also been reported. All studied drugs reduced the cellular content of Ca2+ by 10-20% this was accompanied by a decrease in the contractile force of40-90% [141]. 

In electrically driven guinea-pig atria, callipeltin A induces a positive inotropic effect at concentrations ranging between 0.7 and 2.5 jlM [108,109]. Callipeltin A appears to display an Na-ionophore action, since resting aorta responded to callipeltin A in a dose-dependent manner, with EC50 at 0.44 p,M, which was not inhibited by common calcium channel blockers. Callipeltin A also increased Na efflux of Na-loaded erythrocytes, with EC50 at 0.51 p,M [110]. 

The spasmolytic activity of 7 on isolated guinea-pig ileum was comparable to that of chlorphencyclane 6. They had the same effects on contractility and on refractory period of the left guinea-pig atria, similar antitremorine activity and comparable acute toxicity in mice. The shorter duration of action observed for the sila analogues containing a Si-O-C group may be connected with their hydrolytic inactivation (80AP(313) 129). 

Jordan R, Midgley JM, Thonoor CM, Williams CM. Beta-adrenergic activities of octopamine and synephrine stereoisomers on guinea-pig atria and trachea. J Pharm Pharmacol 1987 39(9) 752-754. 

Intravenous administration of either one of the four pure compounds previously isolated from M. oleifera leaves (niazinin A, niazinin B, niazimicin and niaziminin A + B) in the concentration range of 1-10 mg/kg, produces hypotensive and bradycardiac effects in anaesthetized rats. Pretreatment of the animals with atropine (1 mg/kg) completely eliminates the hypotensive and bradycardiac effects of acetylchohne (ACh), whereas cardiovascular responses to the test compounds remains unaltered, ruling out the possible involvement of muscarinic receptor activation. In isolated guinea-pig atria all the compounds... 

Tolazoline and the structurally related imidazoline tetrahydrozoline may be H2 receptor agonists since tolazoline-induced acid stimulation in the dog can be blocked by burimamide, metiamide and cimetidine and both imidazolines induce characteristic -agonist effects on isolated guinea pig atria preparations which can be blocked by metiamideJ Clonidine, like the imidazolines, has a-adrenergic agonist activity... 

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