Beta-adrenoceptor changes in submandibular glands of old mice

Piantanelli, L.; Fattoretti, Patrizia; Viticchi, C.

doi:10.1016/0047-6374(80)90114-1

Cited by 31 publications

(11 citation statements)

References 16 publications

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“…Though several steps in the signal transduction mechanism can be altered, a major role in age-related changes is played by P-adrenoceptors [3][4][5]. In particu lar, we have previously shown that some altered responsiveness following in vivo stimulation are paralleled by altered receptor density [6][7][8][9][10], Such findings were obtained in submandibular glands and brain cortex of mice. Recently, we directed our attention to the age-related alterations in the regulatory capacity of such receptors [11], In fact, padrenoceptors are dynamic in nature, being continuously regulated by endogenous and exogenous stimuli, that is, they decrease or increase in number according to the pres ence of agents such as drugs and homologous and heterologous hormones [12].…”

supporting

confidence: 48%

“…It has been shown previously that P-adrenoceptor density de creases with advancing age in both the sub mandibular glands [7] and brain cortex [10] of the same strain of mice used in the exper iments presented here. Such a decrease, al treated mice are statistically significant only at 3 months of age (p < 0.05).…”

Section: Discussionmentioning

confidence: 92%

“…Receptor assay was performed as previously re ported [7] using crude membrane preparations sus pended in the incubation buffer described above. Concentrations of DHA ranged from 0.3 to 4 nmol/1 in a final volume of 0.8 ml containing about 0.2 mg of protein.…”

Section: Binding Assaymentioning

confidence: 99%

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Influence of Age on the Thyroid Hormone-Induced Up-Regulation of β-Adrenoceptors in Mouse Brain Cortex

Viticchi¹,

Grinta²,

Piantanelli³

1990

Gerontology

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The influence of ageing on the ability of the brain cortex β-adrenoceptors to be regulated by very short stimulation with thyroid hormones has been investigated. Experiments were performed in 3-, 10-, 17- and 22-month-old mice using both thyroxine (T₄) and triiodothyronine (T₃) as stimulators and analyzing β-adrenergic receptor characteristics 15 and 60 min after hormone injection. Results showed that a statistically significant up-regulation is present in both young and old mice when treated with T₃. On the contrary, after T₄ injection only 3-month-old animals respond to such a short-term treatment, whereas older adult and old animals showed not statistically significant changes. Thus, the impairment in the T₄-induced up-regulation starts already in adult mice and does not seem to further increase progressively with advancing age. From these findings it is suggested that the lack of responsiveness of β-adrenoceptors to T₄ but not to T₃ stimulation in adult and old mice may be due to relatively early impairment in the transformation of T₄ into T₃.

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supporting

confidence: 48%

Section: Discussionmentioning

confidence: 92%

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Influence of Age on the Thyroid Hormone-Induced Up-Regulation of β-Adrenoceptors in Mouse Brain Cortex

Viticchi¹,

Grinta²,

Piantanelli³

1990

Gerontology

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“…The effects and also fate of these antagonists show changes with age (3) that are difficult to explain on the basis ofwhat is known about the age-related features ofthe adrenergic system (1,(4)(5)(6). In this work we studied the regeneration ofreceptors for these antagonists in senescent rats.…”

mentioning

confidence: 99%

Regeneration of beta-adrenergic receptors in senescent rats: a study using an irreversible binding antagonist.

Pitha¹,

Hughes²,

Kusiak³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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The drug used in this study, bromoacetylalprenololmenthane, has the ability to bind and block irreversibly a-adrenergic receptors. The drug was bound to membranes prepared from hearts, lungs, and brains of both senescent and young rats with a similar affinity. When this drug was injected into rats in nontoxic doses (up to 70 mg/kg), up to 90% of P-adrenergic receptors were irreversibly blocked 4 hr after injection, whereas the injection of similar amounts of (±)-alprenolol was without effect on receptor number. In senescent animals this blockade lasted considerably longer than in young animals; receptor numbers in hearts and lungs of senescent rats returned to control levels only 1 month after injection. The number of (3-adrenergic receptors in brains of senescent rats was unaffected by this drug. Thus, based upon the long-lasting blockade of -adrenergic receptors in therapeutically important organs, it appears that irreversible binding blockers may have potential in the treatments ofsenescent organisms.3-Adrenergic antagonists continue to be one of the main medications used to treat hypertension (1)-a symptom afflicting about one-third of a population sample of the elderly in the United States (2). The effects and also fate of these antagonists show changes with age (3) that are difficult to explain on the basis ofwhat is known about the age-related features ofthe adrenergic system (1,(4)(5)(6). In this work we studied the regeneration ofreceptors for these antagonists in senescent rats. Such a study can provide information concerning possible development of longer acting antagonists (7) and may eventually help in the clarification ofage effects on the adrenergic system. Bromoacetylalprenololmenthane, whose structure is given in Fig. 1, was used in this study. It was shown previously that this drug binds, at first reversibly, to a binding site of the p-adrenergic receptor and this reversible complex is transformed rapidly through a chemical reaction into a covalent receptor-drug complex that does not further bind molecules of agonists or antagonists (8). Furthermore, this drug has the advantage of high affinity for 3adrenergic receptors (8), as compared to similar compounds (9). Utilization of this drug in senescent rats revealed that the receptor number in some therapeutically important organs-such as heart and lung-remains below control levels for as long as 1 month after treatment. Thus, in senescence the rate ofregeneration, and probably the rate ofde novo synthesis of receptors, is low. The results point to the possibility of using irreversible blockade to perform "molecular surgery"-i.e., to excise part of the receptors in a senescent organism in a reasonably selective way and in a practically permanent manner. MATERIALS AND METHODSThe senescent animals, unless otherwise stated, were 27-month-old Sprague-Dawley rats that have a 2-yr median lifespan and were obtained from Harlan Industries (Indianapolis, IN). The animals used in the regeneration experiment were divided into groups of (i) drug tre...

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“…It also plays a role in maintenance of synchrony among the major homeostatic networks, i.e., the nervous, the immune, and the neuroendocrine systems [5], which undergo severe alterations during aging. In particular, it was reported that with advancing aging the adrenergic nerve system is strongly impaired [6][7][8]. Interestingly, however, not all the adrenergic alterations are definitive: both ß-adrenoceptor (ßAR) and · 1 -adrenoceptor (· 1 AR) densities, found to be decreased in the brain cortex of old mice when compared with young ones, are recovered when a neonatal thymus is grafted into an old recipient [9].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Mouse Brain Cortex Adrenoceptor in Old Mice by Supplementation of Zinc and Thymomodulin

Viticchi¹,

Moresi²,

Piantanelli

1999

Gerontology

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Background: Previous experiments have shown that the age-related decrease of mouse brain cortex adrenoceptor density can be recovered by grafting a neonatal thymus into old recipients. The question arises whether similar results can also be obtained in the presence of a single thymic factor such as thymomodulin (TMD). It is worth noting that the activity of some thymic factors is strictly zinc (Zn) dependent and that their age-related decreased production is recovered in old mice supplemented with Zn. Objective: The above-mentioned evidences prompted us to verify whether Zn and TMD, either alone or combined, are able to induce some corrective effects on age-dependent alterations of adrenoceptor characteristics of the mouse brain cortex. Methods: Thus, we performed experiments on four groups of Balb/c mice treated with saline, Zn, TMD, or both Zn and TMD. Treatments started when animals were 18 months old and ran for 6 months. The α₁- and β-Adrenoceptor characteristics were assayed by steady state binding analysis using labelled prazosine and iodocyanopindolol, respectively. Data were analyzed using one-way analysis of variance, followed, when appropriate, by multiple-comparison analysis. Results: Results show an increase of β-adrenoceptor density and a decrease of α₁-adrenoceptor density in both Zn- and Zn+TMD-treated animals when compared to saline-treated controls, while receptor affinities did not change significantly. Conclusions: The lack of action of TMD suggests that this type of treatment cannot mimic the effects of grafting the whole gland; it cannot be excluded that different time-dose schedule could be more effective. Zn treatment, on the other hand, does modulate adrenoceptors; however, it shows a corrective action on the age-related decreased density of β-adrenoceptors, but further decreases that of α₁-adrenoceptors. This differential action could be due to their differential physiological role.

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Beta-adrenoceptor changes in submandibular glands of old mice

Cited by 31 publications

References 16 publications

Influence of Age on the Thyroid Hormone-Induced Up-Regulation of β-Adrenoceptors in Mouse Brain Cortex

Influence of Age on the Thyroid Hormone-Induced Up-Regulation of β-Adrenoceptors in Mouse Brain Cortex

Regeneration of beta-adrenergic receptors in senescent rats: a study using an irreversible binding antagonist.

Modulation of Mouse Brain Cortex Adrenoceptor in Old Mice by Supplementation of Zinc and Thymomodulin

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