Drug receptor mechanisms in smooth muscle: beta-chloroethylamine-sensitive and -resistant receptor mechanisms.
Both alpha1-adrenoceptors and M3-cholinoceptors can be divided into two subtypes discriminated by the beta-chloroethylamines, chloroethylclonidine and propylbenzilylcholine mustard (PrBCM), only in the presence of GTP. The full agonists interact with both subtypes to induce responses. The partial agonists activate one of them to induce responses but behave as competitive antagonists when they interact with the other. The responses mediated through the receptors that are activated by the partial agonists are resistant to myosin light chain kinase inhibitors, while the response through the activation of the other receptors are suppressed by the inhibitors. The receptor stimulations through alpha1A-adrenoceptor and PrBCM-sensitive M3-cholinoceptor subtypes mainly activate the myosin light chain-phosphorylation-independent pathway mediated through protein kinase C and low molecular weight GTP-binding protein, whereas the stimulations through alpha1B-adrenoceptors and the PrBCM-phosphorylation-dependent pathway are directly related to Ca2+/calmodulin.
Takayanagi
I
I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Koike
K
K
Satoh
M
M
Okayasu
A
A
D000322:Adrenergic Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011438:Propylbenzilylcholine Mustard / Q000494:pharmacology*; D043587:Receptor, Muscarinic M3; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D015398:Signal Transduction / Q000502:physiology
D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3; D018340:Receptors, Adrenergic, alpha-1; D011976:Receptors, Muscarinic; D011438:Propylbenzilylcholine Mustard; C051731:chlorethylclonidine; D006160:Guanosine Triphosphate; D003000:Clonidine; D002118:Calcium