Biomedical subjects

M A Oriowo

Publications and source records attributed to M A Oriowo.

At least 19 recordsLinked to original sources

PubMed2000

Buspirone, a 5-HT(1A) receptor agonist, dilates the perfused rat uterine vascular bed through alpha(1)-adrenoceptor blockade.

In the perfused rat uterine vascular bed, 5-hydroxytryptamine (5-HT) produced dose-dependent vasoconstrictor responses. Buspirone, a selective 5-HT(1A) receptor agonist, was not effective at low doses but produced a response at high doses. When perfusion pressure was raised with phenylephrine, responses to 5-HT were enhanced while buspirone produced dose-dependent vasodilator responses. Buspirone did not produce vasodilation when perfusion pressure was raised with vasopressin or U46619. Buspirone-induced vasodilator responses were not affected by selective 5-HT(1A) receptor antagonists, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]-decane-7,9-dione (BMY 7378) and N-tert-butyl-3-(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenylpropanamide (WAY 100478), indicating that specific 5-HT(1A) receptors might not be involved in buspirone-induced vasodilation. Buspirone (3 x 10 (-5) M) and prazosin (3 x 10(-9) M) antagonized noradrenaline-induced constriction with dose ratios of 19.1+/-2.9 and 11.7+/-2.1, respectively. The dose ratio of these antagonists in combination was 46.6+/-8.1. Since the combination ratio is closer to the sum of their individual dose ratios less 2 (i.e. DR(p)+DR(b)-2) than it is to the product of their individual dose ratios, our data suggest an interaction of buspirone with alpha(1)-adrenoceptors. Buspirone also protected adrenoceptors against inactivation by phenoxybenzamine confirming that buspirone interacted with alpha(1)-adrenoceptors. We concluded that buspirone-induced vasodilation of the perfused rat uterine vascular bed is mediated through blockade of alpha(1)-adrenoceptors rather than through 5-HT(1A) receptors.

Animals↗

PubMed1999

Inhibitory effect of capsaicin on cholinergic transmission in ovine airways: evidence for non-cholinergic contractions.

Electrical stimulation of ovine trachealis smooth muscle and bronchial ring segments induced neurogenic and monophasic atropine-sensitive contractions. Pretreatment of the tissues with capsaicin (100 microM) significantly reduced these contractions indicating a possible contribution of a peptidergic neurotransmitter to the contractions. The effect of capsaicin on electrically induced contractions was significantly inhibited by capsazepin indicating an action on vanilloid receptors. In both preparations, electrically induced contractions were not modified by tachykinin NK(1)- and NK(2)-receptor antagonists singly and in combination. It was therefore concluded that a component of the atropine-sensitive electrically induced contractions of ovine airways smooth muscles involved the release of a peptide neurotransmitter which is probably not a tachykinin. However, an action of capsaicin on prejunctional vanilloid receptors located on cholinergic nerves cannot be ruled out.

Acetylcholine↗

PubMed1999

Inhibitory effects of cannabinoid receptor ligands on electrically-evoked responses in rat isolated tracheal ring segments.

We have examined the possible existence of cannabinoid receptors in the isolated rat tracheal ring segments by studying the effects of some cannabinoid receptor ligands on electrically-induced contractions. Anandamide (10(-8)-3 x 10(-5)m), an endogenous ligand for cannabinoid receptors, and WIN 55,212-2 (10(-9)-3 x 10(-5)m), a moderately selective CB(2)agonist, inhibited electrically evoked contractions of the rat tracheal ring segments in a concentration-related manner. Addition of phentolamine (10(-6)m) to Krebs Henseleit solution to block alpha(2)-adrenoceptors did not affect anandamide-induced inhibition of the electrically evoked contractions. The EC(25)(-log m) values were 5.25+/-0.2 and 5.8+/-0. 4 for anandamide and WIN 55,212-2, respectively. The maximal inhibition produced by the highest concentration of the agonists used was 51.4+/-5.8% for anandamide and 35.1+/-19.5% for WIN 55, 212-2. WIN 55,212-3 also produced a concentration-dependent inhibition of the electrically evoked contractions. The maximal inhibition produced by WIN 55,212-3 was 15.8+/-2.4. The inhibitory effects of anandamide and WIN 55,212-2 were not attenuated by SR141716A (10(-6)m), a selective CB(1)receptor antagonist. Anandamide (10(-8)-3 x 10(-5)m) did not relax rat tracheal ring segments pre-contracted with carbachol (10(-6)m). These results suggest that anandamide and WIN 55,212-2 produce pre-junctional inhibitory effects in the rat trachea and that these effects were likely mediated through cannabinoid CB(2)receptors. These effects were probably non-cannabinoid receptor-mediated considering the high concentrations of the agents required to produce inhibitory responses and the effectiveness of WIN 55,212-3.

Animals↗

PubMed1999

Source(s) of activator calcium for noradrenaline-induced vasoconstriction in the perfused rabbit isolated ovarian vascular bed: a role for tyrosine kinase.

The effects of Ca2+ withdrawal and agents affecting Ca2+ translocation on alpha1-adrenoceptor-mediated vasoconstrictor responses in the perfused rabbit ovarian vascular bed were studied. Noradrenaline-induced vasoconstriction was lost in a Ca(2+)-free Krebs' solution, and the rate of loss of the response was accelerated by EGTA (2 mM). Noradrenaline-induced vasoconstriction and SDZ NVI 085-induced vasoconstriction were concentration-dependently inhibited by verapamil and nifedipine. These agents were, however, more effective against KCl-induced responses. Cyclopiazonic acid, an intracellular Ca(2+) depletor, concentration-dependently inhibited noradrenaline-induced responses and abolished the response in Ca(2+)-free Krebs' solution. GF 109203X and polymyxin B, inhibitors of protein kinase C (PKC), had no significant effect on noradrenaline-induced responses. Tyrosine kinase inhibitors, genistein and erbstatin, inhibited noradrenaline-induced vasoconstriction in the perfused rabbit ovarian vascular bed. The results would suggest that both extracellular Ca2+ and intracellular Ca2+ participate in noradrenaline-induced vasoconstrictor responses in the perfused rabbit ovarian vascular bed. The results would also suggest that tyrosine kinase and not protein kinase C activation has a role in such effects.

Animals↗

PubMed1999

Beta1- and beta3-adrenoceptors mediate relaxation in ovine trachealis smooth muscle.

Isoprenaline (non-selective) and noradrenaline (beta1-selective) concentration-dependently relaxed ovine tracheal strips precontracted with carbachol. The pD2 values were 7.07 +/- 0.08 and 6.13 +/- 0.10 for isoprenaline and noradrenaline, respectively. In the same preparation, salbutamol either produced weak relaxation or in some cases, contractile responses indicating the presence of very little or no beta2-adrenoceptors in this preparation. Isoprenaline-and noradrenaline-induced relaxations were antagonized by propranolol and atenolol with pA2 values in the range reported in the literature for an action on beta1-adrenoceptors. ICI 118551 also antagonized isoprenaline- and noradrenaline-induced relaxation but at concentrations much higher than are required to block beta2-adrenoceptors, confirming that beta2-adrenoceptors do not contribute significantly to these responses. The selective beta3-adrenoceptor agonist, BRL 37344A produced concentration-dependent relaxation of tracheal strips. BRL 37344A was a full agonist producing 100% relaxation of carbachol-induced tone. BRL 37344A-induced relaxation was weakly antagonized by propranolol confirming an action, mainly, on beta3-adrenoceptors. Cyanopindolol antagonized isoprenaline-induced relaxation (in the presence of propranolol, 10(-7) M) with a pA2 value of 8.06 +/- 0.24. It was therefore concluded that beta1- and beta3-adrenoceptors mediated agonist-induced relaxation in sheep tracheal strips.

Adrenergic beta-Agonists↗

PubMed1999

Alpha1-adrenoceptor antagonist effect of (+/-)-dobutamine in rat isolated gastric artery preparation.

(+/-)-Dobutamine at concentrations < or =10(-5) M did not evoke contractions of rat gastric artery segments. However, when the tissues were contracted with methoxamine, (+/-)-dobutamine evoked concentration-dependent relaxation. The relaxant responses were not significantly affected by propranolol. In the same preparation, propranolol competitively antagonized isoprenaline-induced relaxation with a -log K(B) value of 7.90+/-0.26. (+/-)-Dobutamine did not relax arterial ring segments precontracted with vasopressin (10(-7) M). (+/-)-Dobutamine antagonized noradrenaline-induced contractions of the gastric artery segments. The pA2 value was 6.93+/-0.20, and the slope of the Schild regression line was 1.22+/-0.14. This value (slope) was not significantly different from 1, indicating competitive antagonism. Pretreatment of gastric artery segments with dobutamine before phenoxybenzamine (PBZ) protected against inactivation of alpha1-adrenoceptors by PBZ. The dose ratio of prazosin (3x10(-9) M) and (+/-)-dobutamine (10(-5) M) in combination was close to the expected sum of their individual dose ratios minus 1, indicating interaction with a common site. It was therefore concluded that (+/-)-dobutamine evoked relaxation of rat gastric artery segments by an action not involving beta-adrenoceptor activation but by blocking alpha1-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1999

Functional characterization of beta-adrenoceptors mediating relaxation in sheep gallbladder.

The purpose of this study was to characterize beta-adrenoceptor subtype(s) mediating relaxation in smooth muscle strips of the sheep gallbladder. Experiments were performed on isolated smooth muscle strips suspended in tissue baths containing Krebs' solution. Isoprenaline (10(-8) M-10(-5) M) and salbutamol (10(-7) M-10(-4) M) produced concentration-dependent relaxation of carbachol (10(-7) M-3 x 10(-7) M) contracted smooth muscles of the sheep gall bladder. Isoprenaline-induced relaxation was significantly antagonized by propranolol with -logKB values of 7.81 +/- 0.11 (n = 7) and 7.73 +/- 0.12 (n = 6) in the fundic and ductal strips respectively. Atenolol (10(-5) M), a selective beta 1-adrenoceptor antagonist, also significantly antagonized isoprenaline-induced relaxation with -logKB values of 5.82 +/- 0.11 and 6.09 +/- 0.09 in the fundic and ductal strips respectively. However, ICI 118551, a selective beta 2-adrenoceptor antagonist, at concentrations up to 10(-6) M had little or no effect on isoprenaline-induced relaxation in either of these preparations. BRL 37344A, a selective beta 3-adrenoceptor agonist produced concentration-dependent relaxation of carbachol-precontracted fundic and ductal strips. BRL 37344 was approximately 9-fold more potent in the ductal than fundic strips. In both preparations, BRL 37344-induced relaxation was not significantly (p > 0.05) antagonized by propranolol (3 x 10(-7) M). This would confirm that the response was mediated via beta 3-adrenoceptors. It was concluded that beta 1- and beta 3-adrenoceptors coexist in the sheep gallbladder and mediate smooth muscle relaxation.

Adrenergic beta-Agonists↗

PubMed1999

Biphasic relaxant response of ovine trachealis muscle to electrical field stimulation: influence of cooling.

Electrical field stimulation of ovine trachealis muscle produced neurogenic atropine-sensitive contractions under resting conditions. However, when the tissues were precontracted with 5-hydroxytryptamine in the presence of atropine, electrical field stimulation induced a frequency-dependent tetrodotoxin-sensitive relaxation. The relaxation was biphasic, consisting of fast and slow phases. The fast component was attenuated by propranolol, indicating an action on beta-adrenoceptors. The slow phase was attenuated by capsaicin and, therefore, involved release of a peptide. These results showed that excitatory responses in ovine trachealis muscles are cholinergically mediated, while both adrenergic and peptidergic components mediate electrically induced relaxation in the trachea. We also examined the influence of lowering bath temperature to 20 degrees C on electrically evoked responses. These were significantly reduced by cooling. At 20 degrees C, under resting conditions, the time-to-peak tension was lengthened, and the amplitude of the contractile responses was significantly (p < 0.05) reduced. In the same preparation, carbachol-induced contractions were not reduced by cooling, indicating that the reduction in electrically induced contractions was probably due to a reduction in transmitter release. Cooling also abolished the fast inhibitory phase (adrenergic in nature) without significantly inhibiting the slow (non-adrenergic, non-cholinergic) component. Propranolol (1 micromol/l) and capsaicin (100 micromol/l) did not affect significantly the slow relaxation observed during cooling. It was concluded that cooling inhibited cholinergically mediated, electrically induced contractions and selectively abolished the adrenergic component of electrically induced relaxant responses.

Analysis of Variance↗

PubMed1999

Endothelial modulation of vasoconstrictor responses in the perfused rabbit ovarian vascular bed.

The purpose of this study was to investigate the effects of endothelial denudation, inhibitors of nitric oxide (NO) and prostanoid synthesis on vasoconstrictor responses in the perfused rabbit ovarian vascular. The experiments were conducted using an in vitro perfusion system, where the ovarian vascular bed (en bloc) was perfused with Krebs' solution delivered at a constant flow rate using a peristaltic pump. Changes in perfusion pressure, which reflected peripheral resistance, were measured. Results showed that noradrenaline (NA) (10(-9) to 10(-6) mol) induced reproducible dose-dependent vasoconstrictor responses. Vasoconstrictor effects of low doses of noradrenaline were not affected by perfusion of the vascular bed with CHAPS (4.7 mg/ml for 30 s) to remove the endothelium. The same treatment however, significantly reduced responses induced by the higher doses of noradrenaline, thus depressing the maximum response. KCl-induced vasoconstriction was not affected by CHAPS. L-N(G)-nitroarginine (L-NOARG) (10(-5) mol/l) enhanced NA-induced vasoconstriction. D-NOARG, the inactive isomer of L-NOARG and aminoguanidine, an inhibitor of inducible nitric oxide synthase reduced rather than enhanced noradrenaline-induced responses. Methylene blue (3 x 10(-5) mol/l) and LY 83583 (10(-5) mol/l) produced a potentiation of NA-induced vasoconstrictor responses. Indomethacin (3 x 10(-6) mol/l) did not significantly enhance NA-induced vasoconstriction. The nonselective endothelin antagonist, SB 209670 (10(-7) and 10(-6) mol/l) did not inhibit the vasoconstriction to NA. In conclusion, results are interpreted to suggest that NA-induced vasoconstriction in the perfused rabbit ovarian vascular bed is accompanied by a release of NO and possibly endothelium-derived contracting factor. There was no evidence for a modulation of vasoconstrictor responses by products of arachidonic acid metabolism or endothelins released from the endothelium.

Animals↗

PubMed1998

Histamine receptor subtypes mediating hyperpolarization in the isolated, perfused rat mesenteric pre-arteriolar bed.

Histamine is a general dilator of rat blood vessels. We investigated the relative contribution of receptor subtypes to the rat mesenteric dilator responses initiated by histamine and related agonists. Histamine initiated dose, and endothelium-dependent, dilation of constricted mesenteric beds with an ED50 of 0.4 +/- 0.1 nmol. The ED50 was increased 10-fold by 0.1 microM chlorpheniramine (a histamine H1-receptor selective antagonist). Histamine H2 receptor blockade with tiotidine (0.1 microM) slightly decreased, while thioperamide (1 microM), a selective histamine H3 receptor antagonist, did not block histamine-induced dilation. Mesenteric bed dilation initiated by histamine H2 receptor selective agonists, amthamine and dimaprit, were antagonized markedly by tiotidine. However, the dilation initiated by the putative histamine H3 receptor selective agonists, R(-)- or S(+)-alpha-methylhistamine and imetit were not affected by thioperamide (1 microM). Histamine H2- and H3-receptor mediated dilator effects were endothelium-independent and were blocked by either excess (80 mM) extracellular K+, or 1 mM tetrabutylammonium (a non-selective K+ channel blocker), as well as by 1 microM dequalinium, a non-peptide blocker of the small conductance Ca2+-activated (SKCa) K+ channels. We conclude that (i) histamine H1 receptor subtype predominantly mediates endothelium-dependent dilator effect of histamine, and (ii) vascular hyperpolarization through opening of K+ channels (SKCa) mediate the dilator responses to histamine H2 receptor (amthamine and dimaprit) and the putative histamine H3 receptor (R(-)-alpha-methylhistamine and imetit) agonists.

Animals↗

PubMed1998

Sodium nitroprusside-induced cGMP-independent vasodilator responses in the perfused rabbit ovarian vascular bed.

Sodium nitroprusside (SNP) (10(-9)-10(-6) mol) and carbachol (10(-9)-10(-6) mol) induced dose-dependent vasodilatation in the perfused rabbit isolated ovarian vascular bed. Carbachol, but not SNP-induced vasodilatation was abolished by treatment with CHAPS (4. 7 mg ml-1, 30 s) to remove the endothelium. Carbachol-induced responses were also significantly attenuated by LY 83583 (10(-5) M) and methylene blue (3x10(-5) M). L-NOARG (10(-5) M) reduced carbachol-induced vasodilatation. None of these compounds affected SNP-induced vasodilator responses. Both SNP- and carbachol-induced vasodilatation were attenuated by raising the [K+] in the Krebs' solution to 40 mM. The responses were also reduced by TEA (20 mM) but not by glibenclamide. It was therefore concluded that SNP induced cGMP-independent vasodilator responses in the perfused rabbit ovarian vascular bed. This vasodilator response involved membrane hyperpolarisation since it was lost in high [K+] Krebs' solution. (c) 1998 The Italian Pharmacological Society.

Aminoquinolines↗

PubMed1998

Functional characterization of alpha1-adrenoceptor subtypes in the rabbit spleen.

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.

Acetonitriles↗

PubMed1998

Neural inhibition in the rat lower esophageal sphincter: role of beta 3-adrenoceptor activation.

1. Electrical field stimulation (EFS) of the rat lower esophageal sphincter produced tetrodotoxin-sensitive relaxant responses. 2. The relaxant responses were not significantly affected by propranolol but were attenuated by 6-hydroxydopamine and cyanopindolol, indicating beta 3-adrenoceptor activation. 3. The relaxant responses were significantly reduced in tissues previously exposed to BRL 37344, a beta 3-adrenoceptor agonist. 4. It was concluded that EFS-induced relaxation was adrenergic in origin and was mediated by beta 3-adrenoceptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1998

Heterogeneity of alpha 1-adrenoceptor subtypes mediating noradrenaline-induced contractions of the rat superior mesenteric artery.

The effects of subtype-selective alpha 1-adrenoceptor antagonists on noradrenaline-induced contractions of ring segments of rat superior mesenteric artery were investigated to determine the subtype(s) of alpha 1-adrenoceptors mediating contractions in this preparation. Noradrenaline-induced contractions of rat mesenteric artery ring segments were potently and surmountably antagonized by prazosin, WB 4101 and BMY 7378. Judging from the slopes of the Schild regression lines, which were significantly different from 1, WB 4101 and BMY 7378 behaved as noncompetitive antagonists. Spiperone and 5-methylurapidil were only effective at high concentrations. Chloroethylclonidine (CEC, 100 mumol/l) displaced the noradrenaline concentration-response curve to the right reducing its potency approximately 100-fold. Noradrenaline-induced contractions post-CEC were also antagonized by prazosin. However, prazosin was less potent against these contractions. A 61,603, a selective alpha 1A-adrenoceptor agonist, contracted ring segments of the mesenteric artery. These contractions were antagonized by prazosin, however with a low affinity, indicating interaction with a low-affinity receptor subtype. It was therefore concluded that alpha 1D- and, possibly, alpha 1L-adrenoceptor subtypes mediated noradrenaline- induced contractions of the rat superior mesenteric artery.

Adrenergic alpha-Agonists↗

PubMed1997

Beta(3)-adrenoceptors mediate smooth muscle relaxation in the rat lower oesophageal sphincter.

1. The role of beta(3)-adrenoceptors in isoprenaline-induced relaxation of carbachol-precontracted ring segments of the rat lower oesophageal sphincter (LOS) was examined. 2. Isoprenaline (10(-8)M-10(-5)M) relaxed ring segments of the LOS in a concentration-dependent manner. Propranolol (10(-7)M) had very little antagonist effect on isoprenaline-induced relaxation. 3. Dobutamine (10(-7)M-10(-4)M), salbutamol (10(-7)-10(-4)M) and BRL 37344 (10(-8)-10(-5)M) also relaxed carbachol-contracted ring segments of the LOS in a concentration-dependent manner. The relaxant responses to these agonists were similarly not antagonized by propranolol (10(-7)M). 4. Cyanopindolol (10(-6)M), produced a parallel rightward displacement of isoprenaline, dobutamine, salbutamol and BRL 37344 concentration-response curves with similar potencies. The pKB values range from 7.3 +/- 0.1 to 7.7 +/- 0.2. 5. The relaxant effect of isoprenaline in the rat LOS was not inhibited by NG-nitro-L-arginine (L-NOARG; 3 x 10(-5)M), glibenclamide (10(-5)M) or tetraethylammonium (1 mM). 6. It was concluded that beta(3)-adrenoceptors mediate isoprenaline-induced relaxation in rat lower oesophageal sphincter and that activation of these receptors was not linked to either ATPase-, Ca(2+)-dependent K+ channels or to NO release.

Adrenergic beta-Agonists↗

PubMed1996

Characterization of alpha-adrenoceptor subtype(s) mediating vasoconstriction in the perfused rabbit ovarian vascular bed.

1. alpha 1-Adrenoceptor agonists, noradrenaline, phenylephrine, methoxamine, oxymetazoline and SDZ NVI 085 but not alpha 2-adrenoceptor agonists, UK 14304, tizanidine or clonidine evoked dose-dependent vasoconstriction of the isolated perfused rabbit ovarian vascular bed. The rank order of agonist potency was noradenaline > oxymetazoline > phenylephrine > SDZ NVI 085 > methoxamine. 2. Prazosin (10(-8) M - 10(-5) M) displaced agonist dose-response curves to the right. The pA2/pKB values ranged between 7.27 and 7.66 against noradrenaline, phenylephrine, methoxamine and SDZ NVI 085 and were not significantly different from each other. Prazosin was however significantly less potent against oxymetazoline (pA2 6.38). Yohimbine (10(-6) M - 10(-5) M) was not very effective against any of the agonists. 3. WB 4101 (10(-8) M - 10(-5) M) displaced agonist dose-response curves to the right. The pA2/ pKB values ranged between 7.08 and 7.93 against noradrenaline, phenylephrine, methoxamine and SDZ NVI 085. WB 4101 was significantly less potent against oxymetazoline (pKB 6.85). 4. SZL-49 (5 x 10(-6) M) but not chloroethylclonidine (3 x 10(-5) M) significantly reduced vasoconstrictor responses to all the agonists. 5. Electrical field stimulation of the ovarian bed produced frequency-dependent vasoconstrictor effects which were abolished by 6-OHDA. The responses were also antagonized in a concentration-dependent by prazosin (10(-7) M - 10(-5) M) and WB 4101 (3 x 10(-8) M - 3 x 10(-7) M). Yohimbine reduced the response to electrical stimulation by 20% at 10(-5) M. The vasoconstrictor effect was also inhibited by SZL-49 but not by chloroethylclonidine. 6. These results would suggest that the vasoconstrictor responses of the ovarian vascular bed to adrenergic agonists and to electrical stimulation are mediated via the alpha 1A-adrenoceptor subtype.

Adrenergic alpha-Agonists↗

PubMed1996

The selectivity in vitro of the stereoisomers of the beta-3 adrenoceptor agonist BRL 37344.

The stimulation by BRL 37344 of lipolysis in rat adipose tissues, and of relaxation of the rat distal colon, is mediated by the beta-3 adrenoceptor. The stereochemical requirements of the beta-3 adrenoceptor are poorly understood. The activities of the four stereoisomers of BRL 37344 (i.e., two pairs of diastereoisomers) on three beta-3 adrenoceptor-mediated responses (brown and white adipose tissue lipolysis and relaxation of distal colon) have been determined and compared with those responses mediated by beta-1 adrenoceptors (increase in atrial rate) and beta-2 adrenoceptors (uterine relaxation). The potency order for the stereoisomers (RR>RS=SR>>SS) was the same for all tissues, regardless of whether the response was mediated by beta-1, beta-2 or beta-3 adrenoceptors. These results indicate that both chiral centers are determinants of agonist potency at all three subtypes of the beta adrenoceptor. Furthermore, agonist activity at beta-1, beta-2 and beta-3 adrenoceptors resides predominantly with the RR enantiomer. Finally, the RR enantiomer of BRL 37344 was a more potent agonist in brown adipocytes (EC50 = 3.3 +/- 0.8 nM) than in white adipocytes (EC50 = 5.7 +/- 0.9 nM) or colon (EC50 = 27.5 +/- 7.7 nM).

Adrenergic beta-Agonists↗

PubMed1995

Different atypical beta-adrenoceptors mediate isoprenaline-induced relaxation in vascular and non-vascular smooth muscles.

Atypical beta-adrenoceptors mediating smooth muscle relaxation were compared in several rat tissues including the distal colon, fundic strip, thoracic aorta and common carotid artery. Isoprenaline, CGP 12177 and BRL 37344 concentration-dependently relaxed longitudinal strips of the distal colon and fundus precontracted with carbachol (10(-6)M) as well as ring segments of the aorta and carotid artery precontracted with noradrenaline (10(-7)M). The rank order of potency was isoprenaline = BRL 37344 > CGP 12177 in the distal colon, isoprenaline = CGP 12177 > BRL 37344 in the aorta and carotid artery segments and isoprenaline > BRL 37344 > CGP 12177 in the fundic strip. Pretreatment with BRL 37344 induced a marked desensitization of the distal colon and fundic strips but not the aorta and carotid artery to isoprenaline. In the fundus and distal colon, pretreatment with CGP 12177 (10(-4)M abolished the effect of isoprenaline. Cyanopindolol (10(-6)M) shifted the isoprenaline curve to the right, without reducing the maximum response, in the distal colon fundic strip. -logKB values were 7.44 +/- 0.08 and 7.53 +/- 0.10 in the distal colon and fundic strip respectively. The same concentration of cyanopindolol did not inhibit the relaxant effect of isoprenaline in the aorta and carotid artery segments. It was therefore concluded that atypical beta-adrenoceptors in these preparations were not identical, indicating heterogeneity of atypical beta-adrenoceptors.

Adrenergic beta-Agonists↗