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The Physiology of Adrenergic Systems in the Solitary Tract Nucleus
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
For the most part, investigators have found no effect of microinjection into the NTS of β-adrenoceptor agonists such as isoproterenol.22,28 Nevertheless, one report19 details the findings of a hypotensive and bradycardic effect of isoproterenol when injected into the NTS of the rat. Moreover, these effects could be blocked by intranuclear microinjection of the β antagonist propranolol or the selective β2 antagonist butoxamine, but not the selective β1 antagonist practolol. On the basis of this set of experiments alone, it might appear that a β-adrenoceptor, possibly of the β2 subtype, is involved in hemodynamic regulation in the NTS. These findings must still be regarded with caution, however, as they have not been replicated.
Adrenoceptor Antagonists
Published in Kenneth J. Broadley, Autonomic Pharmacology, 2017
Substitution on the α-carbon of the side-chain reduces activity. However, as with agonists (see Chapter 4), it also confers β2-adrenoceptor selectivity. The α-methyl derivative of DCI is relatively selective for β2-adrenoceptors. Butoxamine, the N-tert-butyl analogue of methoxamine, displays selectivity for certain β2-adrenoceptor-mediated responses, blocking vascular and uterine smooth muscle more than cardiac responses. Note that methoxamine is a selective α-adrenoceptor agonist which also has some β-blocking properties. N-Isopropylmethoxamine is not an α-agonist but produces the same activity in vivo as does methoxamine, to which it is metabolized in the body. Butoxamine, however, is not dealkylated to methoxamine. H35/25 has been used as a selective β2-adrenoceptor antagonist, blocking the depressor responses to isoprenaline but not the cardiac effects. These agents have now been replaced by ICI 118,551 which also bears the α-methyl group and is the most selective β2-antagonist currently available. This compound has widespread use as a pharmacological tool in the classification and characterization of β2-adrenoceptor populations in different organs, but at present has no therapeutic application. The close similarity between structural requirements for agonist and antagonist activity at the α-adrenoceptor suggests that they interact with common regions of the receptor. They probably bridge two or more of the membrane-spanning α-helixes within the cylinder of the receptor itself (see Chapter 13).
Beta-blocker carteolol and oxprenolol produce cutaneous analgesia in response to needle pinpricks in the rat
Published in Neurological Research, 2023
There are four specific experiments (n = 8 in each group). In the first experiment, the effect of beta-blockers (oxprenolol, carteolol, butaxamine, metoprolol, and acebutolol) at a concentration of 18 mM was evaluated. In the second experiment, the dose-response curves of bupivacaine (0.15, 0.28, 0.42, 0.85, and 1.62 μmol), oxprenolol (0.60, 0.75, 1.50, 2.25, 3.00, 5.40, and 6.00 μmol), and carteolol (1.60, 3.00, 4.50, 6.00, 9.00, 10.80, 12.00 μmol) were performed. The effect of oxprenolol (10 mM) and carteolol (20 mM) was compared with that of bupivacaine (2.7 mM). Injection of normal saline acts as a control. In the third experiment, full recovery times of sensory/nociceptive blockade by oxprenolol, carteolol, and bupivacaine under the equipotent doses (ED50s [50% effective doses], ED75s, and ED25s) were evaluated. In the fourth experiment, the effect of drugs (oxprenolol, carteolol, and bupivacaine) alone was compared to the mixture of drugs at ED95 and epinephrine 1:200,000.
Restraint stress induces uterine microenvironment disorder in mice during early pregnancy through the β2-AR/cAMP/PKA pathway
Published in Stress, 2021
Jiayin Lu, Guanhui Liu, Zixu Wang, Jing Cao, Yaoxing Chen, Yulan Dong
Caspase-3, a member of the Caspase family, plays an important role in the activation of apoptosis, which links mitochondria inside the cell with the external death receptor. Uterine ESCs treated with different drugs were collected, and the expression of Caspase-3 in the cells was detected by the WB method. The DMSO-treated group exhibited no significant change in the expression of Caspase-3 compared with that in the control group (p = 0.434). The addition of the β2-AR agonist ISO in vitro significantly increased the expression of Caspase-3, and the expression of Caspase-3 was significantly increased by 163.58% (p < 0.001) compared with that in the control group. These results indicated that ISO induced the activation of Caspase-3 protein during ESC apoptosis. Also, after the addition of the AC agonist FSK, there was no significant change in the expression of Caspase-3 in the cells compared with that in the ISO-treated group (p = 0.684). The addition of the PKA inhibitor H-89 reversed the expression of Caspase-3 induced by ISO and FSK. Compared with that in the ISO-treated group, the expression of Caspase-3 was significantly reduced by 74.27% (p < 0.001). After the cells were treated with the β2-AR blocker butoxamine for 30 min, ISO was applied to the cells for 24 h. Compared with that in the ISO-treated group, the expression of Caspase-3 was significantly decreased by 81.97% (p < 0.001). The process of β2-AR-induced apoptosis in ESCs was mainly achieved through the cAMP/PKA pathway. The MEK inhibitor PD98059 specifically blocked the activation of ERK. Compared with ISO, the addition of the MEK inhibitor PD98059 significantly reduced the expression of Caspase-3 in cells by 60.90% (p < 0.001). The cells were treated with PDTC for 24 h, and then ISO and FSK were added; the expression of Caspase-3 did not increase in ISO + FSK + PDTC group compared with ISO-treated cells. The addition of PDTC significantly decreased the expression of Caspase-3 in the cells by 70.59% (p < 0.001). In conclusion, the activation of β2-AR promoted the apoptosis of ESCs mainly by activating downstream ERK/MAPK signaling through the cAMP/PKA pathway and inducing NF-κB activation, thereby initiating apoptosis (Figure 8(B)).