title: Effect of an alkylating analog of prazosin on alpha-1 adrenoceptor subtypes and arterial blood pressure.
abstract: Previous studies have shown that a chemically reactive analog of prazosin, SZL-49, reduces the alpha-1 adrenoceptor population by a maximum of 60% (Kusiak et al., 1989). These data support the idea that alpha-1 receptor subtypes exist and only one is sensitive to alkylation by SZL-49. In the present study male rats were injected (i.p.) with SZL-49 (0.5-30 mg/kg) and the effects on [3H]prazosin binding, systemic arterial blood pressure and the pressor response to phenylephrine were assessed 24 hr later. SZL-49 treatment decreased the number of [3H]prazosin sites without affecting receptor affinity. The maximal reduction in binding sites was 60% (32 fmol/mg). At doses of 0.5-, 1-, 5- and 10-mg/kg SZL-49 reduced the receptor number to the same level (83 fmol/mg control; 47-60 fmol/mg treated). Injection of SZL-49 had no effect on resting blood pressure. However, drug treatment (0.5 mg/kg and greater) shifted the phenylephrine dose-response curve to the right. The maximal 1-, 5- and 10-mg/kg SZL-49, the ED50 for phenylephrine was approximately the same. Therefore, over a 20-fold range of SZL-49 concentrations no further reduction in receptor number or phenylephrine ED50 was observed. These data support the idea that S2L-49-sensitive and resistant alpha-1 receptors exist in vivo. The alkylation resistant receptor is capable of maintaining resting blood pressure. Furthermore, both receptors appear to be involved in mediating the increase in blood pressure observed with phenylephrine.
authors.affiliation: Department of Pharmacology, University of Kentucky College of Medicine, Lexington.
authors.forename: M T
authors.initials: MT
authors.lastname: Piascik
authors.forename: B T
authors.initials: BT
authors.lastname: Butler
authors.forename: J W
authors.initials: JW
authors.lastname: Kusiak
authors.forename: J
authors.initials: J
authors.lastname: Pitha
authors.forename: J R
authors.initials: JR
authors.lastname: Holtman
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000478:Alkylation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; C051307:SZL 49; D010656:Phenylephrine; D011224:Prazosin