Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenylephrine and (+/-)N-[5-(4,5-dihydro-1-H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetr ahydronaphthalen-1-yl] methanesulphonamide hydrobromide (A 61603) evoked concentration-dependent contractions of the rabbit spleen. These contractions were antagonized by prazosin (10(-8)-10(-7) M) with pA2 values of 8.34+/-0.11 and 8.15+/-0.10 against phenylephrine and A 61603, respectively. In both cases, the slopes of the Schild plots were not significantly (P>0.05) different from 1.0, indicating competitive antagonism. The effects of subtype-selective antagonists WB 4101 [2-(2-6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride] and 5-methylurapidil on agonist-induced contractions were also examined. WB 4101 competitively antagonized agonist-induced contractions; pA2 values were 8.13+/-0.10 and 8.10+/-0.03 against phenylephrine and A 61603, respectively. Corresponding values for 5-methylurapidil were 8.28+/-0.17 and 7.93+/-0.02 against phenylephrine and A 61603, respectively. Tamsulosin and Rec 15/2739 [(8-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl)-3-methy l-4-oxo-2-phenyl-4H-1-benzopyran dihydrochloride] also antagonized phenylephrine- and A 61603-induced contractions with pA2 values of 9.38+/-0.13 and 9.18+/-0.06 (tamsulosin) and 8.41+/-0.12 and 8.34+/-0.11 (Rec 15/2739) against phenylephrine and A 61603, respectively. HV 723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxyethyl) -amino)-propyl)benzene-aceto-nitrile) fumarate) competitively antagonized phenylephrine-induced contractions with a pA2 value of 8.57+/-0.06. Chloroethylclonidine (CEC; 10(-4) M) shifted phenylephrine and A 61603 concentration-response curves to the right, reducing their potencies approximately two- to threefold, while the maximum response was reduced by 8% in both cases. It was therefore concluded that contractions of the rabbit spleen induced by alpha1-adrenergic agonists were mediated predominantly by a relatively CEC-insensitive alpha1-adrenoceptor subtype, possibly the alpha1L-subtype.
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PMID:Functional characterization of alpha1-adrenoceptor subtypes in the rabbit spleen. 977 16

We evaluated the uroselectivity of a series of alpha1-adrenoceptor antagonists by comparing their potency against phenylephrine-induced increases in urethral perfusion pressure and diastolic blood pressure in the anesthetized rabbit and pithed rat. In the rabbit, Rec 15/2739 (N-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]-3-methyl-4-oxo-2-phenyl -4H-1-benzopyran-8-carboxamide) as well as analogs with a chlorine substituent on the methoxyphenyl ring (Rec 15/2869) or this substituent combined with the replacement of the phenyl substituent on the pyran ring by cyclohexyl (Rec 15/3011) were 2-6-fold more potent against the urethral vs. vascular response to phenylephrine. Rec 15/2841 (N-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]-3-methyl-4-oxo-2-cyc lohexy-4H-1-benzopyran-8-carboxamide) was only 1.5-fold more potent against the urethral response. SL 89.0591 and tamsulosin also showed selectivity for the urethral response (2-2.5-fold), while the quinazolines produced equipotent blockade of urethral and vascular responses (selectivity ratio = 0.9-1.1). The urethral selectivities of Rec 15/2739 and its derivatives were confirmed by evaluation of the response to tilt in sedated, hypovolemic rabbits. Phenylephrine challenge assays did not show any of the antagonists, with the exception of terazosin at 300 microg kg(-1), to be uroselective in the rat (selectivity ratios = 0.2-1.5); potentiation of tilt-induced hypotension in the anesthetized rat showed substantial differences from the rabbit, with Rec 15/2739, but not Rec 15/3011 and Rec 15/2841 showing orthostatic effects equivalent to that observed for prazosin. Hence, Rec 15/2739 was uroselective in the rabbit, but not in the rat, while two of its close structural analogs were highly uroselective in both species. An assay for orthostatic activity in the conscious rat yielded different results, showing prazosin and terazosin, but not Rec 15/2739, to cause a reversal of the pressor response to tilt. Hence, the apparent uroselectivity of an alpha1-adrenoceptor antagonist is both species- and assay-dependent.
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PMID:Effects of alpha1-adrenoceptor antagonists on agonist and tilt-induced changes in blood pressure: relationships to uroselectivity. 1040 51

The fossil record demonstrates that mammals re-entered the marine realm on at least seven separate occasions. Five of these clades are still extant, whereas two are extinct. This review presents a brief introduction to the phylogeny of each group of marine mammals, based on the latest studies using both morphological and molecular data. Evolutionary highlights are presented, focusing on changes affecting the sensory systems, locomotion, breathing, feeding, and reproduction in Cetacea, Sirenia, Desmostylia, and Pinnipedia. Aquatic adaptations are specifically cited, supported by data from morphological and geochemical studies. For example, analysis of oxygen isotopes incorporated into fossil tooth enamel indicates whether these mammals foraged in (and, therefore, ingested) fresh water or sea water. Comparisons between groups are made to see if there are any common patterns, particularly relating to adaptations to aquatic life. Results show that aquatic characteristics evolved in mosaic patterns and that different morphological solutions to aquatic conditions were achieved separately in each of these groups. Changes in the axial and appendicular skeleton assist with locomotion for aquatic foraging. Nostril and eye placement modifications accommodate wading versus underwater foraging needs. All groups exhibit aquatic adaptations directly related to feeding, particularly changes in the dentition and rostrum. The earliest representatives of these clades all show morphological features that indicate they were feeding while in the water, suggesting that feeding ecology is a key factor in the evolution of marine mammals.
Anat Rec (Hoboken) 2007 Jun
PMID:Evolution of marine mammals: back to the sea after 300 million years. 1751 41