A heterogeneous population of alpha 1 adrenergic receptors mediates contraction of human corpus cavernosum smooth muscle to norepinephrine.
In this study we investigated the physiological properties and binding characteristics of alpha-1 adrenergic receptor (alpha 1-AR) in human corpus cavernosum (HCC) in order to identify alpha 1-AR subtypes at the functional protein level. Exposure of tissue strips to norepinephrine (NE) caused concentration-dependent contractions that were partially and noncompetitively inhibited by 10 to 100 microM. of chloroethylclonidine (CEC), an alkylating agent that specifically and irreversibly inactivates alpha 1B-AR and alpha 1C-AR subtypes. Norepinephrine-induced contractions were competitively and effectively inhibited with WB 4101, a competitive, high-affinity antagonist for alpha 1A-AR and alpha 1C-AR subtypes. The CEC-insensitive receptor subtypes bound WB 4101 with high affinity, suggesting the presence of alpha 1A-AR in HCC. Binding of [3H]prazosin and 2-[beta-(4-hydroxy-3-[125I]iodophenyl)-ethylaminomethyl]-tetralone ([125I]HEAT) to membranes of HCC treated with or without CEC demonstrated the presence of two subpopulations: a CEC-sensitive receptor population (40 to 50%), which may represent inactivation of the alpha 1B-AR and alpha 1C-AR subtypes, and a CEC-resistant receptor subpopulation, which is probably the alpha 1A-AR subtype. The physiological and biochemical properties of alpha 1-AR in HCC clearly suggest that the NE-induced contraction of HCC smooth muscle is mediated by more than one alpha 1-AR subtype. It is likely that two or possibly three receptor subtypes are involved in mediating the contraction. Further, it is possible that NE-mediated contraction of trabecular smooth muscle requires synergistic receptor-receptor receptor interactions at the second messenger or at the receptor protein level.
Traish
A M
AM
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Netsuwan
N
N
Daley
J
J
Padman-Nathan
H
H
Goldstein
I
I
Saenz de Tejada
I
I
D000477:Alkylating Agents / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010413:Penis / Q000187:drug effects* / Q000502:physiology*; D011224:Prazosin / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*
D000477:Alkylating Agents; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin