A Pharmacological Study of Alpha Adrenergic Receptor Subtypes in Smooth Muscle of Human Urinary Bladder Base and Prostatic Urethra

The aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription–polymerase chain reaction (RT–PCR). ET-1 (a non-selective ET receptor agonist; 10-10 M to 10-6 M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3×10-7 M. Neither IRL1620 nor sarafotoxin S6c (both ETB-selective agonists; 10-10 M to 10-6 M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ETA-selective antagonist; 10-7 M to 10-5 M) produced a marked shift to the right of the ET-1 concentration–response curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA2 = 7.96; slope = 0.95). In contrast, RES701-1 (an ETB-selective antagonist; 10-7 M to 10-5 M) had no effect on the ET-1 concentration–response curve. RT–PCR revealed positive amplification of ETA receptor mRNA fragment, but not ETB. These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ETA receptor, not by the ETB receptor.

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Role of α1-adrenergic receptor subtypes in contractility of the rabbit abdominal aorta in vitro

Acta Veterinaria Brno ◽

10.2754/avb201382030331 ◽

2013 ◽

Vol 82 (3) ◽

pp. 331-336 ◽

Cited By ~ 1

Author(s):

Jan Gnus ◽

Albert Czerski ◽

Stanisław Ferenc ◽

Wojciech Zawadzki ◽

Wojciech Witkiewicz ◽

...

Keyword(s):

Smooth Muscle ◽

Receptor Antagonist ◽

Abdominal Aorta ◽

Adrenergic Receptor ◽

Receptor Subtypes ◽

Organ Bath ◽

Dependent Manner ◽

Receptor Antagonists ◽

Selective Antagonists

Investigation of the effect of α1-adrenergic receptor subtypes on the contraction of the abdominal aorta will allow for more effective treatment of hypertension by use of selective antagonists. The aim of the study was to evaluate the participation of α1-adrenergic receptor subtypes in the contractility of the aortic smooth muscle cells in rabbits. The in vitro experiments were performed in isolated tissue preparations from 30 adult female New Zealand rabbits. The abdominal aortic sections were placed in organ bath chambers and contracted with increasing doses of non-selective α1-adrenergic receptor agonist phenylephrine without pre-incubation or after incubation in α1-adrenergic receptor subtype-selective or non-selective antagonists. Separate sections were incubated with increasing concentrations of antagonists. Phenylephrine caused maximal rise in arterial smooth muscle tone to 4.75 ± 0.47 mN. The most potent in blocking phenylephrine induced contraction was 5-metylurapidil (α1A-adrenergic receptor antagonist) followed by phentolamine and prazosin (non-selective α1-adrenergic receptor antagonists); BMY 7378 (α1D-adrenergic receptor antagonist), cyclazosin and L-765.314 (α1B-adrenergic receptor antagonists) were less effective. All antagonists, except BMY 7378 elicited relaxation of non-precontracted aorta in dose dependent manner. Our results indicate that postsynaptic α1A receptors are the most potent in producing rabbit abdominal aorta contraction, while α1B and α1D subtypes are less effective.

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