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Electrical responses of cultured porcine thyroid cells to adrenergic agents
Abstract:
The membrane potential of cultured porcine thyroid follicular cells depolarized by up to 20 mV from the resting value of about -73 mV on exposure to beta-adrenoceptor agonists. A similar response was induced by TSH or dibutyryl cyclic AMP. alpha-Adrenoceptor agonists were without effect. The receptor subtype was shown to be (at least predominantly) beta 2 by the order of potency for beta-agonists (isoprenaline approximately equal to fenoterol much greater than adrenaline greater than noradrenaline) and by the relative potency of selective beta-antagonists (ICI 118,551 much greater than atenolol). The alpha-agonist phenylephrine had no effect on the TSH response but weakly inhibited the beta-agonist response. Rather than a physiological antagonism between alpha- and beta-adrenoceptor-mediated responses, this effect was shown to be due to the weak beta-antagonist effect of phenylephrine since the alpha-antagonist phentolamine failed to potentiate the depolarizing response to the mixed agonist noradrenaline, and also failed to block the inhibitory action of phenylephrine on the beta-agonist effect. Sensitivity to beta-agonist was enhanced by omission of serum from the culture medium and reduced by exposure to beta-agonists or a high concentration of TSH or dibutyryl cyclic AMP.
Insights
Beta-adrenoceptor agonists, thyroid-stimulating hormone (TSH), and cyclic AMP depolarize porcine thyroid cells. This response is mediated by the beta-2 adrenoceptor subtype, not alpha-adrenoceptors.
Area of Science:
- Endocrinology
- Cell Physiology
- Pharmacology
Background:
- Thyroid follicular cells play a crucial role in hormone production.
- Adrenergic receptors and thyroid-stimulating hormone (TSH) are known modulators of thyroid function.
- Understanding the specific signaling pathways involved is essential for comprehending thyroid cell regulation.
Purpose of the Study:
- To investigate the effects of adrenoceptor agonists on the membrane potential of cultured porcine thyroid follicular cells.
- To identify the specific adrenoceptor subtypes involved in mediating these effects.
- To explore the relationship between adrenoceptor-mediated responses and TSH signaling.
Main Methods:
- Measurement of membrane potential changes in cultured porcine thyroid follicular cells.
- Application of various beta- and alpha-adrenoceptor agonists and antagonists.
- Stimulation with TSH and dibutyryl cyclic AMP (a cAMP analog).
- Assessment of agonist potency and antagonist selectivity.
Main Results:
- Beta-adrenoceptor agonists, TSH, and dibutyryl cyclic AMP induced a significant depolarization of thyroid follicular cells.
- The response was predominantly mediated by the beta-2 adrenoceptor subtype, as evidenced by agonist potency and antagonist selectivity.
- Alpha-adrenoceptor agonists had no significant effect on membrane potential or TSH response.
- Phenylephrine exhibited a weak beta-antagonist effect, not physiological antagonism.
- Cell sensitivity to beta-agonists varied with culture conditions and prior exposure to agonists or TSH.
Conclusions:
- Beta-adrenoceptor activation, particularly via the beta-2 subtype, leads to depolarization of porcine thyroid follicular cells.
- TSH and cyclic AMP signaling pathways mimic the depolarizing effect of beta-adrenergic stimulation.
- There is no significant physiological antagonism between alpha- and beta-adrenoceptor-mediated responses in these cells.
- Modulation of beta-adrenoceptor sensitivity is influenced by the cellular environment and prior stimulation.