Dependence of prejunctional β-adrenoceptor facilitation of sympathetic neurotransmission on stimulus train length and agonist exposure time

Lakhlani, Parul P.; Eikenburg, Douglas C.

doi:10.1016/0014-2999(93)90418-h

Cited by 4 publications

(5 citation statements)

References 13 publications

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“…To our knowledge, this is the first study to demonstrate an increase in the functional activity of the facilitatory presynaptic ␤ 2 -receptor in the LV in response to pressure overload. Presynaptic ␤ 2 -receptors facilitating NE release have been previously demonstrated in the rat heart (3,6,31) and human atria (42). Results from this study demonstrate an enhanced functional responsiveness of the presynaptic ␤ 2 -receptor to exogenous agonist stimulation after pressure overload.…”

Section: Discussionsupporting

confidence: 69%

“…For studies to examine the presynaptic effects of salbutamol (1-1,000 nM), slices were electrically stimulated at 0.5 Hz for 2 min (total, 60 pulses). The stimulation conditions (0.5 Hz for 2 min) were chosen based on previous results that demonstrated optimal detection of ␤ 2-receptor facilitation of NE release at stimulations of lower frequency (6,31). Moreover, the ␣ 2-receptor antagonist yohimbine was included in the superfusion buffer of all slices based on previous studies, which demonstrated that autoregulation through the ␣ 2-adrenergic receptor effectively masked ␤2-adrenergic regulation of evoked NE release (6,31).…”

Section: Methodsmentioning

confidence: 99%

“…The stimulation conditions (0.5 Hz for 2 min) were chosen based on previous results that demonstrated optimal detection of ␤ 2-receptor facilitation of NE release at stimulations of lower frequency (6,31). Moreover, the ␣ 2-receptor antagonist yohimbine was included in the superfusion buffer of all slices based on previous studies, which demonstrated that autoregulation through the ␣ 2-adrenergic receptor effectively masked ␤2-adrenergic regulation of evoked NE release (6,31). For studies to examine presynaptic ANG II receptors in LV slices from control rats, slices were electrically stimulated (5 Hz for 2 min; total, 600 pulses) in the absence (S1) and presence (S2) of either ANG II (10 nM), losartan (1 M, AT 1receptor antagonist), or ANG II (10 nM) plus losartan (1 M).…”

Section: Methodsmentioning

confidence: 99%

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Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload

Akers¹,

Cassis²

2004

American Journal of Physiology-Heart and Circulatory Physiology

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Activation of the sympathetic nervous system is well documented in heart failure. Our previous studies demonstrated an increase in evoked norepinephrine (NE) release from left ventricle (LV) slices at 10 days of pressure overload. The purpose of this study was to test the hypothesis that presynaptic modulation of NE release contributes to sympathetic activation after pressure overload. We examined the functional status of the presynaptic alpha(2)- and beta(2)-receptors and ANG II subtype 1 (AT(1)) receptors in LV slices from 10-day aortic constricted (AC) and sham-operated (SO) rats. Evoked (3)H overflow from LV slices preloaded with [(3)H]NE was increased in AC rats. The alpha(2)-agonist UK-14,304 decreased evoked (3)H overflow with no differences between groups. The beta(2)-agonist salbutamol increased evoked (3)H overflow with greater sensitivity in slices from AC rats. The beta-antagonist propranolol decreased evoked (3)H overflow from LV slices of AC rats but not controls. ANG II increased evoked (3)H overflow with greater sensitivity in slices from AC rats. These data support the hypothesis that aberrant presynaptic modulation of catecholamine release contributes to sympathetic activation after pressure overload.

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Section: Discussionsupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload

Akers¹,

Cassis²

2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…Effects of the non-selective P-adrenoceptor agonist, isoprenaline, on neurotransmitter overflow Exposure of the kidney to the non-selective P-adrenoceptor agonist, (-)-isoprenaline, results in dose-dependent facilitation of S-I neurotransmitter overflow (Figure 1). The tissue was exposed to each agonist concentration for 2 min to avoid desensitization of prejunctional P-adrenoceptors (Lakhlani & Eikenburg, 1993). The maximum facilitatory response was 93 ± 6% while the EC50 concentration was 1.2 nM (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…The tissue was exposed to each agonist concentration for 2 min to avoid desensitization of prejunctional P-adrenoceptors (Lakhlani & Eikenburg, 1993). The maximum facilitatory response was 93 ± 6% while the EC50 concentration was 1.2 nM (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Pharmacological characterization and anatomical localization of prejunctional β‐adrenoceptors in the rat kidney

Lakhlani

Amenta

Napoleone

et al. 1994

British J Pharmacology

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1 The subtype and anatomical localization of P-adrenoceptors mediating facilitation of stimulusinduced overflow of noradrenaline ('prejunctional P-adrenoceptors') are not conclusively known to date.The present study was undertaken to characterize these receptors by use of pharmacological methods as well as to define their localization (prejunctional or postjunctional) with radio-ligand binding and autoradiography techniques combined with surgical denervation of the sympathetic innervation to the rat kidney.2 Exposure of the kidney to (-)-isoprenaline, the nonselective P-adrenoceptor agonist, resulted in a dose-dependent facilitation of stimulus-induced neurotransmitter overflow. This response was inhibited by propranolol, the f,-and P2-adrenoceptor antagonist, with a pA2 of 9.20 suggesting that the prejunctional P-adrenoceptors are not of the P3-subtype. 3 The rank order of potency and potency ratios of P-adrenoceptor agonists at renal prejunctional P-adrenoceptors (EC50 for agonist/EC50 for (-)-isoprenaline) were: (-)-isoprenaline (1) >procaterol (2) > salbutamol (3) >adrenaline (10) > (+)-isoprenaline (25). However, dobutamine, the Pf-adrenoceptor agonist, failed to enhance stimulus-induced overflow of noradrenaline. These results are indicative of the presence of P2-adrenoceptors as prejunctional ,-adrenoceptors. 4 Facilitation elicited by (-)-isoprenaline and procaterol, the selective P2-adrenoceptor agonist, was inhibited by ICI 118,551, the selective P2-adrenoceptor antagonist, with pKb values of 9.20 and 9.35, respectively at renal prejunctional P-adrenoceptors. Similarly, the pKb values of metoprolol, the selective fi-adrenoceptor antagonist, at renal prejunctional P-adrenoceptors were determined to be 6.25 and 6.18 against (-)-isoprenaline and procaterol, respectively. These results suggest the presence of a homogeneous population of P2-adrenoceptors as prejunctional P-adrenoceptors. 5 Radio-ligand binding analysis of renal P-adrenoceptors revealed the prevalence of the fi,-subtype as compared to the P2-subtype (63% vs 37%). However, surgical denervation of the rat kidney, resulting in more than 90% reduction in renal noradrenaline content, selectively reduced the P2-adrenoceptor population by 80%, implying the presence of P2-adrenoceptors on renal sympathetic nerve terminals.6 Autoradiographic analysis demonstrated the presence of P,-adrenoceptors on cortical structures such as glomeruli and tubules. fi2-Adrenoceptors were found to be present on tubules (minor population), collecting tubules in outer medulla and the adventitia and adventitial-medial border of intraparenchymal branches of the renal artery. Surgical denervation of the rat kidney resulted in the disappearance of P2-adrenoceptors associated with the intraparenchymal branches, without affecting the P-adrenoceptor populations at other sites. These results support the notion that the P2-subtype is present on renal sympathetic nerve terminals and demonstrate that these prejunctional P2-adrenoceptors are associated with the renal vasculature ...

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Fine Tuning of Sympathetic Transmitter Release via Ionotropic and Metabotropic Presynaptic Receptors

Boehm

Kubista

2002

Pharmacological Reviews

196

154

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The release of transmitters at sympathoeffector junctions is not constant, but subject to modulation by a plethora of different mechanisms. In this respect, presynaptic receptors located on the sympathetic axon terminals are of utmost importance, because they are activated by exogenous agonists and by endogenous neurotransmitters. In the latter case, the transmitters that activate the presynaptic receptors of a nerve terminal may be released either from the very same nerve ending or from a different axon terminal, and the receptors involved are auto- and heteroreceptors, respectively. In terms of their structural and functional features, receptors of sympathetic axon terminals can be categorized as either ionotropic (transmitter-gated ion channels) or metabotropic (most commonly G protein-coupled) receptors. This review summarizes results on more than 30 different metabotropic and four different ionotropic receptors that have been found to control the amount of transmitter being released from sympathetic neurons. Each of these receptors may not only stimulate, facilitate, and reduce sympathetic transmitter release, respectively, but also interact with the functions of other receptors present on the same axonal varicosity. This provides a multitude of mechanisms that regulate the amount of sympathetic transmitter output. Accordingly, a sophisticated cross-talk within and between extra- and intracellular signals is integrated at axon terminals to adapt the strength of sympathoeffector transmission to a given situation. This will not only determine the function of the sympathetic nervous system in health and disease, but also therapeutic and untoward effects of drugs that bind to the presynaptic receptors in sympathetically innervated tissues.

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Dependence of prejunctional β-adrenoceptor facilitation of sympathetic neurotransmission on stimulus train length and agonist exposure time

Cited by 4 publications

References 13 publications

Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload

Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload

Pharmacological characterization and anatomical localization of prejunctional β‐adrenoceptors in the rat kidney

Fine Tuning of Sympathetic Transmitter Release via Ionotropic and Metabotropic Presynaptic Receptors

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