Description of robotically assisted single-site transabdominal preperitoneal (RASS-TAPP) inguinal hernia repair and presentation of clinical outcomes.

BACKGROUND: The aim of our study is to report our initial clinical experience with robotically assisted single-site transabdominal preperitoneal (RASS-TAPP) hernia repair, to verify the safety and efficacy of the procedure and to describe the surgical procedure. METHODS: We retrospectively reviewed all patients undergoing RASS-TAPP at our institution from March 2013 through December 2013. Data regarding patient demographics, type and location of hernia, operative time and clinical outcomes were collected and analyzed. RESULTS: Fourty five hernias were repaired in 34 patients (30M, 4F) by a single surgeon. The mean age was 49.3 years and mean BMI was 26.5. 31 lateral defects, 13 medial defects and 1 femoral defect were repaired. Three patients presented with recurrent hernias and nine had bilateral defects. The mean operative time for all cases was 80.5 min and for all unilateral hernias 69 min. Considering just the unilateral hernias without any additional procedures, operative time was 63 min. The mean follow-up time was 5.5 months. There has been one superficial surgical site infection, but no observed clinical recurrence or neuralgia to date. CONCLUSION: Robotically assisted single-site transabdominal preperitoneal hernia repair is safe and effective. The absence of clinical evidence of recurrence or neuralgia is encouraging and should promote further study.

Pharmacological characterization of alpha1-adrenoceptor subtypes in the bovine tail artery.

Ioudina, M. V., Dyer, D. C. Pharmacological characterization of alpha1-adrenoceptor subtypes in the bovine tail artery. J. vet. Pharmacol. Therap. 25, 363-369. The purpose of this study was to identify the alpha1-adrenoreceptor subtypes present in the bovine tail artery which mediate contractions to adrenergic agonists. A61603, an alpha1A-selective agonist, was more potent compared with norepinephrine and phenylephrine. The pKA value of A61603 was 6.93 +/- 0.19 microM (n=6). Antagonists, BMY 7378, WB 4101 and 5-methylurapidil, caused a parallel shift to the right of the concentration-response curve to A61603 with pA2 values of 6.62, 9.27 and 8.86, respectively. Prazosin, BMY 7378 and WB 4101 inhibited phenylephrine induced contraction with pA2 values of 9.47, 7.17 and 9.73, respectively. The pA2 values obtained for 5-methylurapidil, WB 4101, BMY 7378 and prazosin against alpha1-adrenoceptor agonists were significantly correlated with pKi values (Zhu, Zhang & Han, 1997, Eur. J. Pharmacol.329, 55-61) for the cloned alpha1a-adrenoceptor but not with the cloned alpha1b- or alpha1d-adrenoceptor. BMY 7378, a selective alpha1D-adrenoceptor antagonist, was significantly more potent against the nonsubtype selective agonist phenylephrine than to A61603. Chloroethylclonidine (50 microM for 10 min) did not affect contractile responses to A61603, but caused a significant inhibition of contractile responses to phenylephrine. In conclusion, it appears that alpha1A- and alpha1D-adrenoceptors play a role in adrenergic mediated contraction in the bovine tail artery.

Heterogeneity and complexity of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein.

To understand the subtypes of alpha 1-adrenoceptors in the regulation of uterine and umbilical vascular function, the subtypes of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein were investigated pharmacologically. The use of the irreversible alpha 1B-adrenoceptor antagonist, chloroethylclonidine, revealed the heterogeneity of alpha 1-adrenoceptors in these two tissues. Chloroethylclonidine showed different patterns of action. While it depressed the maximal contraction to norepinephrine in the umbilical vein, it did not decrease the maximal response in the uterine artery. The alpha 1A-adrenoceptor antagonist, 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane (WB 4101), competitively inhibited norepinephrine-induced contractile responses in the ovine uterine artery and umbilical vein with intermediate pA2 values of 8.30 and 8.45, respectively. Combined use of chloroethylclonidine with either prazosin or WB 4101 produced an additive inhibition of norepinephrine-induced contractions in both tissues, suggesting an interaction of WB 4101 with a chloroethylclonidine-insensitive alpha 1-adrenoceptor. However, the chloroethylclonidine-insensitive alpha 1-adrenoceptor differed on the affinity for prazosin in the uterine artery and umbilical vein. The Ca2+ channel blocker, nifedipine, inhibited contractions to both the chloroethylclonidine-sensitive alpha 1-adrenoceptor (alpha 1B subtype) and the chloroethylclonidine-insensitive alpha 1-adrenoceptor in both tissues. Prazosin, WB 4101 and chloroethylclonidine all inhibited norepinephrine-induced contraction due to the release of calcium from intracellular stores in both tissues. Our results suggest that there is heterogeneity and complexity of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein. Both the chloroethylclonidine-sensitive and insensitive alpha 1-adrenoceptor may use both intracellular and extracellular Ca2+ sources.

5-Hydroxytryptamine stimulates phosphoinositide hydrolysis and contraction in the ovine umbilical artery.

5-Hydroxytryptamine-stimulated contraction and generation of inositol phosphates (InsPs) were investigated in isolated ovine umbilical artery from near term pregnant sheep. 5-Hydroxytryptamine produced a concentration-dependent contraction in the presence or absence of external Ca2+, however, the contractile response in Ca(2+)-free medium was depressed by 67% (P < 0.05). The initial increase of either inositol monophosphate (InsP1) or inositol bisphosphate (InsP2) was not apparent, although a significant rise in both InsP1 and InsP2 was observed at 30 min (107 and 100% over basal level, P < 0.05). The generation of inositol trisphosphate (InsP3) was rapid and reached its peak at 60-90 s (35% over basal level, P < 0.05), followed by a second rise at 30 min (96% over basal level, P < 0.05). The generation of InsPs stimulated by 5-hydroxytryptamine was also concentration-dependent. In agreement with previous contraction studies, the generation of InsPs stimulated by 5-hydroxytryptamine was blocked by 10 nM ketanserin, a specific 5-HT2A receptor antagonist. A temporal study revealed that the generation of InsP3 coincided with the phasic component of the contractile response induced by 5-hydroxytryptamine. Our results suggest that through activation of 5-HT2A receptors, the generation of InsP3 plays a critical role in the contraction induced by 5-hydroxytryptamine in the ovine umbilical artery.

Pharmacological characterization of alpha-adrenoceptors in the bovine median caudal artery.

This study was initiated to characterize alpha-adrenoceptors in the isolated bovine median caudal (tail) artery preparation for use as a model of blood vessels in the extremities of cattle. Prazosin shifted the concentration-response relationship for noradrenaline and phenylephrine to the right with pA2 values of 8.74 and 9.04, respectively. Against noradrenaline, phentolamine yielded a pA2 of 7.36. The concentration-response relationship for medetomidine was not inhibited by rauwolscine or idazoxan. The noradrenaline KA was 3.11 microM. These results suggest that catecholamines elicit alpha-adrenoceptor-mediated contractions primarily through alpha1-adrenoceptors and not alpha2-adrenoceptors.

Pharmacological characterization of alpha 1-adrenoceptors in porcine uterine artery.

This study was undertaken to ascertain if changes in the affinity to alpha 1-adrenoceptor agonists and antagonists could explain the increase in uterine artery vasoconstriction to adrenergic stimuli during the luteal phase of the estrous cycle in pigs. We also sought to determine the subtype(s) of adrenoceptor (alpha 1A and alpha 1B) in the porcine uterine artery. When phenylephrine was the agonist, uterine artery pA2 values for prazosin were 8.98, 9.04 and 9.10 in the luteal and follicular phases and in early pregnancy, respectively. The KA (dissociation constant) values for phenylephrine were 6.5, 3.7 and 4.4 (microM) in the luteal and follicular phases and in early pregnancy, respectively. The use of the putative alpha 1A-adrenoceptor WB4101 (2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxane ) and the alpha 1B-adrenoceptor antagonist chloroethylclonidine indicated that both alpha 1A- and alpha 1B-adrenoceptors are present in the porcine uterine artery and that a similar magnitude of inhibition of responses to noradrenaline by each of the antagonists occurred in arteries from the luteal and follicular phases and in early pregnancy. This suggests that the alpha 1A:alpha 1B adrenoceptor ratio does not vary significantly during the estrous cycle and in early pregnancy. This study indicates that porcine uterine artery alpha 1-adrenoceptor affinity is similar in the luteal and follicular phases of the estrous cycle and in early pregnancy.

Pharmacokinetics of atenolol in clinically normal cats.

OBJECTIVES: To determine the pharmacokinetics of atenolol (AT) after i.v. and oral administrations in cats, to assess duration of beta-blocking effect, and to determine whether AT can be effectively used once per day. ANIMALS: 9 clinically normal cats. PROCEDURE: Single doses of 1 (i.v.) or 3 (oral) mg of AT/kg of body weight were administered to each cat on different occasions, and serial blood samples were collected. Plasma concentrations of AT were subsequently determined, using high-performance liquid chromatography. The plasma concentration data were analyzed, using noncompartmental analysis. An isoproterenol challenge test was used to determine the beta-blocking effect of AT on heart rate after 3 consecutive days of oral treatment (3 mg/kg, once a day). RESULTS: After i.v. administration, mean +/- SD apparent volume of distribution at steady state and systemic clearance values were 1,088 +/- 148 ml/kg and 259 +/- 72 ml/h/kg, respectively. Bioavailability was 90 +/- 9% after oral administration. The half-life values were 3.44 +/- 0.5 and 3.66 +/- 0.39 hours after i.v. and oral administrations, respectively. Compared with baseline values prior to AT administration, heart rates at 6 and 12 hours after administration of AT were significantly reduced. CONCLUSIONS: AT has high oral bioavailability in cats, resulting in small interindividual variability in its kinetics in this species. The drug has beta-blocking effect in cats, as indicated by the attenuated heart rate response to isoproterenol; this effect persists for at least 12 hours in clinically normal cats.

5-Hydroxytryptamine induces endothelium-independent relaxations of sheep pulmonary vein: role of cyclic nucleotide.

5-Hydroxytryptamine produced concentration-dependent relaxations in isolated sheep pulmonary vein, which were insensitive to removal of the endothelium. 5-Hydroxytryptamine stimulated concentration-dependent increases of cyclic AMP levels in the pulmonary vein, and there was a significant linear correlation between relaxations elicited by 5-hydroxytryptamine and tissue cyclic AMP formations. The soluble guanylate cyclase inhibitor methylene blue (10 microM) failed to block 5-hydroxytryptamine-induced relaxations. The results suggest that 5-hydroxytryptamine-induced relaxations of sheep pulmonary vein are mediated, at least in part, by increases of tissue cyclic AMP levels.

Pharmacokinetics of propofol in mixed-breed dogs and greyhounds.

Pharmacokinetics and recovery characteristics of propofol in Greyhounds and mixed-breed dogs were compared. In all dogs, disposition of propofol was adequately described by a 2-compartment open model, with a rapid distribution phase followed by a slower elimination phase. When findings in Greyhounds were compared with those in mixed-breed dogs, significant differences were observed in mean concentrations of propofol in blood, recovery characteristics, and estimates for apparent volume of distribution, volume of distribution at steady state, and total body clearance. In addition, Greyhounds recovered from anesthesia at higher concentrations of propofol than did mixed-breed dogs. A secondary peak in blood propofol concentration was observed in 8 of 10 Greyhounds and in 5 of 8 mixed-breed dogs. This peak corresponded to the time of return of the righting reflex.

Evidence that ergovaline acts on serotonin receptors.

Ergovaline is a potent vasoconstrictor of isolated bovine uterine and umbilical arteries. Contractions to ergovaline were slow to develop and required 120 min or more to reach their maximum effect. Tissues contracted to ergovaline did not relax over a 3 hr period despite repeated changing of the bath fluid with fresh Krebs solution. This indicates a high affinity of ergovaline for its tissue receptor. Contractions to ergovaline were antagonized by ketanserin and phenoxybenzamine but not by prazosin or phentolamine. This indicates that 5-HT2 receptors but not adrenergic receptors are involved in the vasoconstriction. The results suggest that drugs effective in blocking 5-HT2 receptors may be useful in preventing or reducing the toxic symptoms due to ergovaline in animals consuming Acremonium coenophialum infected tall fescue.

Lysergic acid diethylamide is a partial agonist at 5-HT2 receptors in ovine uterine artery of late pregnancy.

d-Lysergic acid diethylamide (LSD) produced dose-dependent contractions (EC50, 17.9 +/- 2.1 nM) on isolated ovine uterine artery of late pregnancy, which were competitively antagonized by ketanserin. The maximal contraction to LSD was 51% of the 5-HT response. LSD competitively antagonized (pA2 9.21) contractions produced to 5-hydroxytryptamine (5-HT). The results indicate that LSD is a partial agonist at 5-HT2 receptors in ovine uterine artery.

Effect of R(-)2,5-dimethoxy-4-methylamphetamine on uterine and umbilical blood flow in conscious pregnant sheep.

Pregnant sheep and their fetuses were instrumented between 110 to 120 days of gestation (term, 145 days) for monitoring maternal and fetal arterial blood pressure, heart rate and blood flow in the maternal uterine and fetal intra-abdominal umbilical arteries. The administration of 2,5-dimethoxy-4-methylamphetamine (DOM, a 5-HT2 agonist) i.v. to the ewe in doses ranging from 1 to 20 micrograms/kg of ewe body weight produced dose-dependent decreases in the blood flow of the uterine and umbilical arteries. This was accompanied by an increase in the arterial blood pressure of the mother and fetus and a decrease in the fetal heart rate. DOM significantly increased the vascular resistance to blood flow in the uterine and umbilical arteries. The maximal increase in the vascular resistance of the uterine and umbilical arteries was 19.6- and 2.6-fold, respectively. Ketanserin, a 5-HT2 antagonist (1 mg/kg), administrated 30 min prior to DOM significantly inhibited the reduction in blood flow in the uterine and umbilical arteries to DOM and blocked the increased vascular resistance in these vessels. The inhibitory effects of ketanserin on the responses to DOM in the uterine and umbilical arteries were surmountable. Our results indicate that DOM is a potent constrictor of the uterine and umbilical vasculature which may lead to fetal distress as evidenced by a decrease in fetal heart rate and arterial blood PO2. 5-HT2 receptor stimulation by DOM may be involved in these effects since they were blocked by ketanserin.

Characterization of alpha-adrenoceptors mediating contraction in isolated ovine umbilical vein.

Responses to alpha-adrenoceptor agonists were studied in isolated umbilical vessels obtained from fetal lambs within 2 weeks of term (term = 145 days). Norepinephrine produced concentration-dependent contractions of the umbilical vein, but not in the umbilical artery. The contraction elicited by norepinephrine in the umbilical vein was not potentiated by cocaine (10(-5) M). Epinephrine also produced contractions of the umbilical vein with a potency similar to that of norepinephrine. Phenylephrine was less potent than norepinephrine while clonidine and xylazine were inactive in producing contractions of the umbilical vein. The dissociation constant (KA) of norepinephrine in the umbilical vein was 172 +/- 41 nM. There was little, if any, alpha-adrenoceptor reserve in the umbilical vein. Contraction produced to norepinephrine in the umbilical vein was effectively blocked by prazosin and phentolamine. Yohimbine was 500 times less potent than prazosin in blocking norepinephrine-induced contraction in the umbilical vein. Idazoxan only minimally antagonized the contractions elicited to norepinephrine. We conclude that alpha 1-adrenoceptors are present and mediate vasoconstriction in the ovine umbilical vein and that alpha 2-adrenoceptors are not present in this tissue.

5-HT2 receptor-stimulated calcium influx in ovine uterine artery in late pregnancy.

The effects of 5-hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) on the Ca2+ influx in the ovine uterine artery in late pregnancy have been studied by measuring 45Ca2+ uptake. Both 5-HT and DOM (2.5 x 10(-8) M to 2.5 x 10(-5) M) induced concentration-dependent rises in 45Ca2+ uptake in the ovine uterine artery, from a basal level of 30.5 +/- 3.5 muMoles/kg wet tissue to peak levels of 91.1 +/- 9.2 and 84.2 +/- 8.1 muMoles/kg wet tissue, respectively. The Ca2+ influx evoked by 5-HT and DOM was inhibited by ketanserin in a concentration-dependent manner. Methiothepin (2.5 x 10(-7) M) also inhibited 5-HT-induced (2.5 x 10(-6) M) Ca2+ influx by 86%. No antagonism was found with 2.5 x 10(-6) M of 3-tropanyl-3,5-dichlorobenzoate (MDL 72222). The contraction elicited to 5-HT (10(-6) M) and DOM (10(-6) M) was blocked by D600 (10(-6) M) which also blocked the contraction produced to KCl (9 x 10(-2) M). Amrinone (10(-5) M) had no inhibitory effect on these contractions. In accord with the results of the contraction study, D600 (2.5 x 10(-6) M) blocked the Ca2+ influx stimulated by 5-HT (2.5 x 10(-6) M) and amrinone (2.5 x 10(-5) M) failed to inhibit 5-HT-induced Ca2+ influx. Nifedipine (2.5 x 10(-6) M) did not antagonize the influx of Ca2+ induced by 5-HT. Sodium nitroprusside inhibited the 5-HT-induced Ca2+ influx, indicating that at least part of its inhibitory effect on the vasoconstriction evolved by 5-HT is due to the inhibition of the influx of Ca2+.

Vasodilatory effects of nifedipine, methoxyverapamil, and sodium nitroprusside on contractile responses of the ewe uterine artery at term pregnancy.

The differential inhibitory effect of the vasodilators on contractile responses to norepinephrine, serotonin, and potassium on isolated uterine artery ring segments from pregnant ewes within 2 weeks of term was quantified and correlated with the source of Ca++ for the vasoconstrictors producing the smooth muscle contraction. The contraction evoked by the vasoconstrictors was dependent on extracellular Ca++ and in agonist-induced contractions also on an intracellular pool of Ca++. Nifedipine effectively inhibited K(+)-induced (90 mmol/L) contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.95 +/- 0.9 x 10(-8) mol/L), whereas it was relatively ineffective in blocking norepinephrine-induced (10(-5) mol/L) or serotonin-induced (10(-5) mol/L) vasoconstriction (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.38 +/- 0.4 x 10(-4) mol/L and 2.04 +/- 0.4 x 10(-5) mol/L, respectively). Methoxyverapamil (D-600) strongly inhibited serotonin-induced contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 3.3 +/- 0.3 x 10(-7) mol/L). The phasic rather than the tonic components of the serotonin- and norepinephrine-induced contractions were more effectively inhibited by D-600 (p less than 0.05). Sodium nitroprusside preferentially blocked (p less than 0.05) the sustained tonic components of norepinephrine- and serotonin-induced vasoconstrictions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 7.1 +/- 0.4 x 10(-7) mol/L and 8.2 +/- 0.6 x 10(-7) mol/L, respectively). On the basis of these findings it is concluded that D-600 and sodium nitroprusside are more effective than nifedipine in blocking contractile responses due to receptor stimulation, and therefore might be more effective in the treatment of hypertensive emergencies in which these amines might be implicated.

Characterization of serotonergic receptors mediating contraction of ovine umbilical artery.

Responses to serotonergic agonists were studied in isolated umbilical arteries obtained from fetal lambs within 2 weeks of term. The order of potency of the agonists was determined to be 2,5-dimethoxy-4-methyl-amphetamine (DOM) greater than 5-hydroxytryptamine (5-HT) greater than alpha-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine = m-trifluoromethyl-phenylpiperazine greater than 8-hydroxy-dipropylaminotetralin greater than 2-methyl-5-HT greater than 1-(2-methoxyphenyl) piperazine. Variations in the sensitivity and potency of the agonists results primarily from the variation in the affinity for the 5-HT2 receptor and less so in the efficacy, alpha-Methyl-5-HT was a full agonist compared to 5-HT. The others were partial agonists. The mean KA values for 5-HT and DOM were 4.71 +/- 0.62 x 10(-7) and 0.36 +/- 0.04 x 10(-7) M, respectively. Contractions to 5-HT and DOM were antagonized by ketanserin with pA2 values being 9.4 and 9.1, respectively, suggesting that they act on the same receptor and that their responses are mediated by 5-HT2 receptors. Contractile responses to 8-hydroxy-dipropylaminotetralin, 2-methyl-5-HT and the phenylpiperazines [m-trifluoromethyl-phenylpiperazine and 1-(3-chlorophenyl) piperazine] were also blocked by ketanserin (10(-8) M), indicating that contractions produced by these agonists were mediated by 5-HT2 receptors. No antagonism by MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) of responses to 5-HT indicates that 5-HT3 receptors are not present in this tissue.

Receptor mechanisms for 5-hydroxytryptamine (5-HT) in isolated ovine umbilical vein.

5-Hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) produced a concentration-dependent contraction in isolated umbilical veins obtained from fetal lambs within 2 weeks of term. Contractions to 5-HT were antagonized by ketanserin, mianserin and methiothepin with the dissociation constants (KB) being 2.17 +/- 0.36, 1.37 +/- 0.55 and 1.98 +/- 0.48 nM, respectively. The order of potency of serotonergic agonists in this tissue was: DOM greater than 5-HT greater than alpha-methyl-5-HT greater than 1(3-chlorophenyl) piperazine (mCPP) greater than m-trifluoromethyl-phenylpiperazine (TFMPP) greater than 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) = 2-methyl-5-HT. alpha-Methyl-5-HT was a full agonist compared to 5-HT. DOM possessed greater affinity but less efficacy than that of 5-HT. The affinities and efficacies of the other agonists studied were lower than those of 5-HT. Variation in the sensitivity and potency of agonists is primarily due to variations in their affinity for 5-HT receptors. Assessment of receptor occupancy vs. functional response demonstrated very little, if any, receptor reserve for 5-HT receptors in this tissue. Contractile responses to DOM, 8-OH-DPAT, mCPP and 2-methyl-5-HT were effectively blocked by ketanserin. The dissociation constants (KB) of ketanserin against these agonists were as follows: DOM, 2.78 +/- 0.85 nM; 8-OH-DPAT, 3.47 +/- 1.12 nM; mCPP, 1.45 +/- 0.51 nM; 2-methyl-5-HT, 1.99 +/- 0.74 nM. The dissociation constant of MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) vs. 5-HT was 13833 nM. No antagonism by prazosin (10(-7) M) or yohimbine (10(-7) M) of the responses to 5-HT was observed. These results indicate that 5-HT2 receptors are present in the ovine umbilical vein. 5-HT3 receptors were not present in this tissue. Activation of alpha-adrenoceptors was not involved in the contractions to 5-HT.

Characterization of 5-hydroxytryptamine receptors on isolated ovine uterine artery in late pregnancy.

5-Hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) are potent agonists on isolated ovine uterine arteries in late pregnancy. Similar pA2 values (8.56 and 8.33, respectively) of ketanserin, tested against 5-HT and DOM, indicate that responses produced by both agonists are mediated by the 5-HT2 receptor. The contractions produced by 8-OH-DPAT and 2-methyl-5-HT were also blocked by ketanserin (10(-8) M) with the dissociation constants (KB) being 2.49 and 2.88 nM, respectively. This provides evidence that these agonists are activating 5-HT2 receptors in the ovine uterine artery. DOM was more potent than 5-HT, but had a similar efficacy to that of 5-HT. The greater affinity of DOM may explain its greater potency. The dissociation constants (KA) of 5-HT and DOM acting on 5-HT receptors were determined by analysis of concentration-response data before and after fractional inactivation of receptors with dibenamine. The mean KA values for 5-HT and DOM were 3.7 +/- 0.7 x 10(-7) and 1.8 +/- 0.3 x 10(-7) M, respectively. Assessment of receptor occupancy vs. functional response demonstrated little or no receptor reserve in this tissue. Several other 5-HT receptor agonists caused contractions but were much less potent than 5-HT. The order of potency of these agonists was determined to be DOM greater than 5-HT greater than or equal to alpha-methyl-5-HT much greater than 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) greater than 2-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine (mCPP) greater than m-trifluoromethyl-phenylpiperazine (TFMPP).(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of alpha-adrenoceptors in the late pregnant ovine uterine artery.

Ring segments of uterine artery from pregnant ewes within two weeks of term were used to study alpha-adrenoceptor-mediated contractions in vitro. The order of potency for the agonists giving the same maximum contractile effect was norepinephrine greater than epinephrine greater than phenylephrine much greater than methoxamine; whereas the maximum contraction to clonidine was about 42% of that to norepinephrine. Medetomidine caused inconsistent responses and B-HT 920 was ineffective. Phentolamine (10(-7) M) and prazosin (10(-7) M), significantly (P less than 0.005) inhibited epinephrine-induced contractions, whereas yohimbine (10(-7) M) was ineffective. Clonidine-induced contractions were blocked by prazosin (10(-8) and 10(-7) M) but were insensitive to yohimbine (10(-7) M). The dissociation constant (KB) of the competitive antagonist prazosin was determined with phenylephrine. The slope of the Schild plot was not significantly different from unity. The pA2 value of prazosin with phenylephrine was 9.1 +/- 0.2. The dissociation constant (KA) and the relationship between receptor occupancy and response for the full agonists norepinephrine and phenylephrine were analyzed using the irreversible antagonist dibenamine. The KA values of norepinephrine and phenylephrine were 1.5 +/- 0.4 x 10(-6) M and 2.5 +/- 0.8 x 10(-6) M, respectively. The occupancy response relationship was nearly linear and the half-maximal response to norepinephrine or phenylephrine was obtained with a 50% receptor occupancy. These results suggest that contraction to alpha-adrenoceptor agonists in the late pregnant ovine uterine artery is mediated primarily by alpha 1-adrenoceptors, and there appears to be no substantial alpha 1-adrenoceptor reserve in this tissue. The mediation of contraction via alpha 2-adrenoceptors is not prominent in this tissue.

Pharmacokinetics of oxytetracycline in the turkey: evaluation of biliary and urinary excretion.

Oxytetracycline (OTC) pharmacokinetic values in plasma and bile were ascertained after IV administration of the drug. At 6 hours after administration of 1 mg of OTC/kg of body weight, 2.15% of the dose was found in the bile and 37.6% was found in the urine. At 2 hours after administration, the peak bile-to-plasma OTC concentration ratio was 60:1. Bioavailability of OTC was 47.6% when it was administered orally to fasted turkeys and was 9.4% when administered to fed turkeys.