Desensitization of α1 Adrenoceptor-Stimulated Glycogen Phosphorylase Activity in Vascular Smooth Muscle

Muñoz, Eric R.; Tsujimoto, Gozoh; Tsujimoto, Aiko; Azhar, Salman; Hoffman, Brian B.

doi:10.1097/00005344-198908000-00014

Cited by 3 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior in vitro exposure and withdrawal of contractile agonists such as histamine, phenylephrine, and carbachol may desensitize smooth muscle to depolarizing stimuli for prolonged periods (6,8,14,15,17,23). Our findings regarding the putative involvement of a Ca 2ϩdepleted SR in heterologous desensitization of carotid media to depolarizing stimuli can be summarized as follows.…”

Section: Discussionmentioning

confidence: 97%

Minor role of a Ca²⁺-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K⁺

Wardle

Murphy

1998

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Exposure of porcine carotid artery smooth muscle (PCASM) to histamine was followed by a large reduction in the rate of force generation in response to 40 mM KCl. This was shown to be a manifestation of slow attainment of a steady-state myoplasmic Ca2+concentration ([Ca2+]i). We hypothesized that if net transsarcolemmal Ca2+ flux into the depolarized PCASM cells is the same before and after a desensitizing histamine treatment, then the transient attenuation of the increase in [Ca2+]imay be due to accelerated uptake of Ca2+ by a partially depleted sarcoplasmic reticulum (SR) acting as a Ca2+ sink or superficial buffer barrier. We tested this hypothesis by eliciting responses of “desensitized PCASM” to 40 mM KCl in the presence of cyclopiazonic acid (CPA), an SR Ca2+-ATPase inhibitor. Contractions of CPA-treated tissues were attenuated less than those of tissues not treated with CPA, but they were not abolished. CPA-insensitive mechanism(s) dominated the desensitization. We conclude that histamine pretreatment reduced net transsarcolemmal Ca2+ flux into PCASM in response to 40 mM KCl.

show abstract

Section: Discussionmentioning

confidence: 97%

Minor role of a Ca²⁺-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K⁺

Wardle

Murphy

1998

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

Appearance of alpha 1-adrenergic receptors in soleus muscles from SHR

Pickar

Gray

Carlsen

1992

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

The depressed functional capabilities of spontaneously hypertensive rat (SHR) muscles, reported previously (Exp. Neurol. 95: 249-264, 1987), may reflect a decrease in muscle responsiveness to catecholamines occurring as a consequence of exposure to the elevated level of plasma catecholamines in SHR. Responsiveness to applied catecholamines was determined in SHR and Wistar-Kyoto rat (WKY) soleus by measuring muscle resting membrane potentials (RMP) in vitro. Epinephrine (10(-6) M) produced a similar membrane hyperpolarization in SHR and WKY fibers. Pretreatment with the beta-antagonist propranolol completely blocked the epinephrine-induced hyperpolarization in WKY, but not in SHR. SHR soleii from both young and old rats contained a population of alpha 1-adrenergic receptors also associated with membrane hyperpolarization. The alpha-receptors appeared to be associated with a ligand-gated Ca(2+)-influx pathway, since the alpha-agonist-induced membrane hyperpolarization required the presence of Ca2+ in the extracellular medium. The alpha-induced hyperpolarization was also blocked by apamin, a derivative of bee venom which blocks a Ca(2+)-activated K(+)-efflux pathway in a variety of tissues. The possible role of these novel alpha-receptors in skeletal muscle function, and their relationship to the development of hypertension, is uncertain.

show abstract

Mechanisms of alpha 1-adrenergic vascular desensitization in conscious dogs.

Kiuchi

Vatner

Uemura

et al. 1992

Circulation Research

View full text Add to dashboard Cite

To investigate the mechanisms of alpha 1-adrenergic vascular desensitization, osmotic minipumps containing either saline (n = 9) or amidephrine mesylate (AMD) (n = 9), a selective alpha 1-adrenergic receptor agonist, were implanted subcutaneously in dogs with chronically implanted arterial and right atrial pressure catheters and aortic flow probes. After chronic alpha 1-adrenergic receptor stimulation, significant physiological desensitization to acute AMD challenges was observed, i.e., pressor and vasoconstrictor responses to the alpha 1-adrenergic agonist were significantly depressed (p < 0.01) compared with responses in the same dogs studied in the conscious state before pump implantation. However, physiological desensitization to acute challenges of the neurotransmitter norepinephrine (NE) (0.1 micrograms/kg per minute) in the presence of beta-adrenergic receptor blockade was not observed for either mean arterial pressure (MAP) (30 +/- 7 versus 28 +/- 5 mm Hg) or total peripheral resistance (TPR) (29.8 +/- 4.9 versus 28.9 +/- 7.3 mm Hg/l per minute). In the presence of beta-adrenergic receptor plus ganglionic blockade after AMD pump implantation, physiological desensitization to NE was unmasked since the control responses to NE (0.1 micrograms/kg per minute) before the AMD pumps were now greater (p < 0.01) than after chronic AMD administration for both MAP (66 +/- 5 versus 32 +/- 2 mm Hg) and TPR (42.6 +/- 10.3 versus 23.9 +/- 4.4 mm Hg/l per minute). In the presence of beta-adrenergic receptor, ganglionic, plus NE-uptake blockade after AMD pump implantation, desensitization was even more apparent, since NE (0.1 micrograms/kg per minute) induced even greater differences in MAP (33 +/- 5 versus 109 +/- 6 mm Hg) and TPR (28.1 +/- 1.8 versus 111.8 +/- 14.7 mm Hg/l per minute). The maximal force of contraction induced by NE in the presence or absence of endothelium was significantly decreased (p < 0.05) in vitro in mesenteric artery rings from AMD pump dogs compared with saline control dogs. Furthermore, alpha 1-adrenergic receptor density, as determined by [3H]prazosin binding in membrane preparations from vessels in the mesentery, was decreased (8.2 +/- 1.0 versus 18.4 +/- 1.4 fmol/mg protein, p < 0.001) without any change in Kd in the AMD pump dogs compared with the saline pump dogs.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

Desensitization of α1 Adrenoceptor-Stimulated Glycogen Phosphorylase Activity in Vascular Smooth Muscle

Cited by 3 publications

References 0 publications

Minor role of a Ca²⁺-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K⁺

Minor role of a Ca²⁺-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K⁺

Appearance of alpha 1-adrenergic receptors in soleus muscles from SHR

Mechanisms of alpha 1-adrenergic vascular desensitization in conscious dogs.

Contact Info

Product

Resources

About

Desensitization of α1 Adrenoceptor-Stimulated Glycogen Phosphorylase Activity in Vascular Smooth Muscle

Cited by 3 publications

References 0 publications

Minor role of a Ca2+-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K+

Minor role of a Ca2+-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K+

Appearance of alpha 1-adrenergic receptors in soleus muscles from SHR

Mechanisms of alpha 1-adrenergic vascular desensitization in conscious dogs.

Contact Info

Product

Resources

About

Minor role of a Ca²⁺-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K⁺

Minor role of a Ca²⁺-depleted sarcoplasmic reticulum in heterologous desensitization of smooth muscle to K⁺