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Biomedical subjects

L Rivera

Publications and source records attributed to L Rivera.

At least 55 records · Page 3Linked to original sources

Heterogeneity of muscarinic receptors in lamb isolated coronary resistance arteries.

1. In vitro experiments in a microvascular myograph were designed to characterize postjunctional muscarinic receptors producing contraction both in the presence and absence of the endothelium in coronary resistance arteries (normalized diameter of 150-450 microns), isolated from the left ventricle of hearts from 3-6 month old lambs. Preferential muscarinic receptor antagonists were used to determine the receptor subtype: pirenzepine (M1 receptor), AFDX 116 (M2 receptor), 4-DAMP and pFHHSiD (M3 receptor). 2. The rank order of potency for muscarinic agonist-induced increases in tension in endothelium-intact preparations was oxotremorine-M = methacholine = acetylcholine (ACh) > carbachol. Removal of the endothelium increased the potency of ACh, but this procedure did not change either the sensitivity or maximal response to carbachol. 3. The contractile response to ACh was reproducible. Incubation with 3 x 10(-7)-3 x 10(-6) M pirenzepine induced non-parallel rightward shifts and depressed the maximum of the concentration-response curve to ACh in endothelium-intact arteries. The slope by Schild analysis was 2.9 +/- 0.8 (P < 0.05, n = 7). Atropine, AFDX 116, 4-DAMP and pFHHSiD produced parallel rightward shifts of the curves to ACh and the slopes of the Schild plots were not significantly different from unity. The pKB values for the antagonists from plots constrained to unity in endothelium-intact segments were: atropine (9.4), 4-DAMP (9.0), pFHHSiD (7.9) and AFDX 116 (6.2). 4. In endothelium-denuded arteries, pirenzepine, AFDX 116 and pFHHSiD caused concentration-dependent, parallel rightward displacements of the concentration-response curves to ACh and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following pKB values: pFHHSiD (8.7), pirenzepine (7.5) and AFDX 116 (6.2). 5. In the presence of the endothelium, low concentrations of pirenzepine (10(-9)-10(-7) M) produced leftward shifts of the ACh concentration-response curves. This potentiating effect of pirenzepine was reversed by endothelial cell removal. In preparations precontracted with the thromboxane-mimetic, U46619, the putative M1-selective agonist, McN-A-343, induced a biphasic relaxation with log IC50 of 8.53 +/- 0.14 and 5.02 +/- 0.08 for the first and second phase of the relaxation, respectively, and maximal relaxations of 22.8 +/- 4.3% and 41.1 +/- 5.4% (n = 16). McN-A-343 relaxed the vessels in the presence of 10(-7) M pFHHSiD and 3 x 10(-7) M AFDX 116, but not after incubation with 10(-9) M pirenzepine. 6. It is concluded from the pKB values for the antagonists used, that contraction induced by ACh in lamb coronary resistance arteries, in either the presence or the absence of the endothelium, is mediated via the M3 subtype of muscarinic receptors, while muscarinic receptors of another subtype at the endothelium seem to modulate the contractile response to ACh.

Acetylcholine↗

Different muscarinic receptor subtypes mediating the phasic activity and basal tone of pig isolated intravesical ureter.

1. We have studied the effects of muscarinic cholinoceptor agonists and specific antagonists on both phasic activity and basal tone of the isolated intravesical ureter of the pig by means of isometric techniques in vitro. 2. Acetylcholine in the presence and absence of physostigmine increased both phasic activity and basal tone of ureteral strips in a concentration-dependent manner. Moreover carbachol, methacholine and oxotremorine-M increased both contractile parameters while bethanechol and McN-A-343 evoked only increases in tone without affecting the frequency of the phasic contractions. 3. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M), failed to modify the contractions evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic antagonist, atropine inhibited both phasic and tonic responses. 4. The muscarinic M1 (pirenzepine), M2 (AF-DX 116 and methoctramine), M3 (4-DAMP, HHSiD and p-F-HHSiD), and putative M4 receptor (tropicamide) antagonists significantly reversed increases in both frequency of phasic activity and baseline tone induced by a submaximal dose of carbachol (10(-5) M). The pIC50 values for inhibition of the induced phasic activity were: atropine (10.16) > 4-DAMP (9.12) > HHSiD (8.22) = methoctramine (7.98) = p-F-HHSiD (7.88 > tropicamide (7.62) = pirenzepine (7.53) = AF-DX 116 (7.45) and for inhibition of basal tone were: atropine (10.73) > 4-DAMP (9.32) > HHSiD (8.65) = pirenzepine (8.43) = p-F-HHSiD (8.38) > methoctramine (7.79) > tropicamide (7.53) > AF-DX 116 (7.04). 5. The antagonist profile indicates that an M1 receptor mediates the tonic response while the phasic activity could involve either both M2 and M3 or an M4 muscarinic receptor. These results suggest that different muscarinic receptor subtypes mediate the phasic and tonic contractile activity induced by a submaximal concentration of carbachol in the porcine intravesical ureter.

Animals↗

Mediation of contraction and relaxation by alpha- and beta-adrenoceptors in the ureterovesical junction of the sheep.

The effects of alpha- and beta-adrenoceptor agonists and antagonists were studied in the sheep ureterovesical junction. Non-specific adrenergic agonists such as adrenaline and noradrenaline induced contraction in the sheep ureterovesical junction, suggesting a predominance of alpha-over beta-adrenoceptors in this functional unity. An inhibition of the noradrenaline-induced contraction was observed after prior blocking with prazosin (10(-7) M) and yohimbine (10(-7) M), the effect of prazosin being more potent than that of yohimbine. The effect of phenylephrine on alpha 1-adrenoceptors was more potent than that of B-HT 920 on alpha 2-adrenoceptors. Isoproterenol caused a concentration-dependent relaxation that was inhibited by propranolol (10(-6) M), pafenolol (10(-5) M) and butoxamine (10(-5) M). These results suggest that ureterovesical junction contraction is mediated by both alpha 1 and alpha 2-adrenoceptors, alpha 1 predominating over alpha 2. Relaxation is mediated by beta-adrenoceptors of the beta 1 and beta 2 subtypes.

Adrenergic alpha-Agonists↗

Mediation of contraction by cholinergic muscarinic receptors in the ureterovesical junction.

1. The muscarinic receptor profile of the sheep ureterovesical junction has been studied by means of in vitro techniques. The relative potency (pD2 = -log EC50) and maximum effect (Emax) observed with carbachol were 51-fold and 25% greater than with acetylcholine respectively. This could be due to the presence of active acetylcholinesterase in this tissue. 2. The pA2 values obtained with the muscarinic antagonists were pirenzepine (8.52), AF-DX 116 (8.05), 4-DAMP (9.41) and hexahydroxiladifenidol (8.66). The slope values of Schild plots were not significantly different from unity, indicating competitive antagonism. Furthermore, when the slopes were constrained to 1, no significant differences were found between the pA2 values. These pA2 values were similar to those observed in other mammalian smooth muscles. 3. It is concluded that muscarinic receptors in the sheep ureterovesical junction smooth muscle belong to the M1, M2 and M3 subtypes and mediate contraction of the ureterovesical junction, which suggests that during parasympathetic stimulation they might prevent vesicoureteral reflux.

Animals↗

Noradrenaline modulates smooth muscle activity of the isolated intravesical ureter of the pig through different types of adrenoceptors.

1. We have studied the effects of alpha- and beta-adrenoceptor agonists and antagonists on both phasic peristaltic activity and basal tone of the isolated intravesical ureter of the pig by means of isometric techniques in vitro. 2. Spontaneous phasic activity was exhibited by 21% of pig intravesical ureter preparations manifested as rhythmic contractions with average frequency and amplitude of 2.54 +/- 0.18 min-1 and 1.48 +/- 0.16 g (n = 31), respectively. 3. Adrenaline, noradrenaline and phenylephrine induced concentration-dependent increases in both phasic activity and basal tone of ureteral preparations, all three agonists being more potent in modifying ureteral phasic activity than baseline tone. B-HT 920, B-HT 933 and clonidine had no significant effect. 4. Phentolamine (10(-9)-10(-7) M) and prazosin (3 x 10(-11)-3 x 10(-8) M) significantly inhibited increases in both frequency of phasic activity and baseline tone induced by a submaximal dose of noradrenaline. Rauwolscine (10(-9)-10(-7) M) affected only the tone evoked by noradrenaline and higher concentrations of this antagonist were needed to block phasic activity. 5. Pretreatment of ureteral strips with the beta-adrenoceptor antagonist, propranolol (10(-6) M), significantly increased the maximum contraction evoked by noradrenaline. After incubation with phentolamine (10(-6) M), noradrenaline (10(-7)-10(-6) M) decreased phasic activity induced by prostaglandin F2 alpha (10(-5) M). Isoprenaline and salbutamol also abolished PGF2 alpha-induced phasic activity. Pafenolol (10(-6) M) and butoxamine (10(-6) M) blocked the inhibitory effect of noradrenaline, isoprenaline, and salbutamol on PGF2 alpha-induced phasic activity. 6. These results suggest that noradrenaline may modulate both phasic peristaltic activity and basal tone of pig intravesical ureter through both alpha- and beta-adrenoceptors.

Adrenergic alpha-Agonists↗

Distribution and function of cholinergic receptors in the sheep detrusor muscle.

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.

Acetylcholine↗

Alpha- and beta-adrenoceptors in the sheep urinary bladder.

A study was undertaken to determine the presence and distribution of alpha- and beta-adrenoceptors in the sheep bladder body and base. In the bladder body, noradrenaline and isoproterenol induced relaxation which was significantly inhibited by propranolol, pafenolol and butoxamine. In the presence of propranolol (10(-5) M), noradrenaline induced a small contraction, as well as phenylephrine, but B-HT 920 failed to cause any effect on the bladder body. In the bladder base, noradrenaline caused a contraction that was significantly inhibited by prazosin but not by yohimbine. Phenylephrine also induced a contractile response in this structure which was inhibited by prazosin. Isoproterenol caused a relaxation that was significantly inhibited by propranolol and pafenolol but not by butoxamine. Relaxation was mediated by both beta 1 and beta 2-adrenoceptors in the detrusor muscle and by beta 1-adrenoceptors in the bladder base. Alpha 1-adrenoceptors contributed to maintain the detrusor tone and contract the bladder base.

Adrenergic beta-Antagonists↗

Mechanisms implicated in the histamine response of the sheep ureterovesical junction.

The isotonic response of the sheep ureterovesical junction to histamine receptor agonists and antagonists was studied in vitro. Histamine (10(-7)-10(-4) M) produced a concentration-dependent contraction which was dependent on the extracellular calcium concentrations. Nifedipine (10(-9)-10(-6) M) partially inhibited the contractile response to histamine. 2-Methylhistamine and 2-pyridylethylamine elicited contractile effect in a concentration-related manner. The order of potency was histamine greater than 2-methylhistamine greater than 2-pyridylethylamine. Dimaprit and 4-methylhistamine produced no response in this tissue. The histamine contraction was antagonized by mepyramine, the pA2 value being 8.41, but not by cimetidine (10(-4) M). Scopolamine (10(-5) M) and indomethacin (10(-6) M) had an inhibitory effect. Phentolamine (10(-5) M), propranolol (10(-7)) and hexamethonium (10(-6) M) did not alter the histamine-induced contractions. The present results indicate that the response to histamine in sheep ureterovesical junction is mediated mainly by a direct action on the smooth muscle through excitatory histamine H1-receptors and partly by an indirect action via the stimulation of intramural cholinergic nerves.

Animals↗

Composition of the parotid saliva in Chilean children with Down's syndrome.

Parotid gland saliva was collected from three groups of Chilean human subjects: Down syndrome, non-Down mentally retarded, and normal individuals. Their salivary flows, pH and electrolyte concentrations were determined. Variables were subjected to ANOVA statistical tests that showed no differences between Down and control groups in salivary flow, pH, chloride, sodium and bicarbonate concentrations. The potassium concentration in the saliva from Down syndrome patients was significantly lower than that of control individuals. Student's t-tests showed significant differences between Down syndrome individuals and controls for potassium and sodium. These last differences may be indicative of a characteristic trait of the trisomic state or of the syndrome itself.

Adolescent↗

Alpha 2-mediated effect of dopamine on the motility of the chicken esophagus.

Dopamine (DA), apomorphine and B-HT 933 produced dose related contractions on isolated longitudinal strips of chicken esophagus, whereas phenylephrine elicited no effect. DA induced contractions of myogenic origin, these contractions were insensitive to DA antagonists and were partially suppressed by yohimbine, which suggested an alpha 2-adrenergic implication in this DA effect. This hypothesis was further investigated by performing binding experiments, in which B-HT 933 displaced the binding of [3H]DA to esophageal homogenates. The results suggest the participation of an alpha 2-adrenergic receptor in the contractile response elicited by DA in the isolated chicken esophagus.

Adrenergic alpha-Agonists↗

Autonomic innervation of the equine urinary bladder.

The distribution and density of intrinsic autonomic nerve fibers and cells were studied in the equine urinary bladder by means of the peroxidase-antiperoxidase immunohistochemical method to localize tyrosine-hydroxylase (TH), and by means of a histochemical technique to detect acetylcholinesterase (AChE) activity. The results suggest that the equine urinary bladder, like that of other mammalian species, possesses a rich autonomic innervation which includes catecholaminergic and acetylcholinesterase positive nerves. At least a part of these nerve fibers have an intrinsic origin from ganglion cell bodies within the bladder wall.

Animals↗

Corneal nerves contain intra-axonal HSV-1 after virus reactivation by epinephrine iontophoresis.

Experimental ocular models of herpes simplex virus type 1 (HSV-1) reactivation have been used to monitor viral shedding in the tear film and the appearance of corneal epithelial lesions, but the temporal correlation between reactivation and the presence of viral particles in the corneal nerves has not been made. Two New Zealand white rabbits were inoculated with 20 microliters of HSV-1 McKrae strain (5.0 x 10(6) PFU/ml) in each eye. Beginning on postinfection day 82, ocular iontophoresis (0.8 mAmps for 8 min) of 0.01% epinephrine was done once a day for 3 consecutive days to induce reactivation. Ten limbal nerves from four corneas processed for transmission electron microscopy contained 883 unmyelinated and 40 myelinated axons. Seven nerves were positive for virus. Viral particles were found only in unmyelinated axons, and in low frequency (24/883). Virus was not found in Schwann cells, perineurium, or adjacent stroma nor were virus particles seen exiting axons. No enveloped virions were found. Axons from six nerves of four control corneas from rabbits with latent, but not reactivated, HSV-1 did not contain virus particles. Induction by corneal iontophoresis of epinephrine suggests that HSV-1 is translocated from the ganglion to the cornea through axonal transport mechanisms. For the first time, evidence of anterograde, intra-axonal transport of HSV-1 particles in response to epinephrine reactivation is demonstrated.

Animals↗

Influence of the autonomic nervous system in the horse urinary bladder.

alpha and beta-adrenergic receptors in detrusor muscle and bladder base of horses were investigated by in vitro responses of smooth muscle strips to exogenous agonist and antagonist drugs. Noradrenaline, isoprenaline and salbutamol induced relaxation of detrusor muscle strips which was significantly inhibited by propranolol and butoxamine suggesting that the response is mediated by beta-2 adrenergic receptors. In the urinary bladder base noradrenaline, phenylephrine and B-HT 920 induced strong contractile effects. These contractile responses were inhibited by the alpha antagonist phenoxybenzamine, the alpha-1 selective antagonist prazosin and the alpha-2 selective antagonist yohimbine. The inhibitory action of prazosin was more potent than that observed with yohimbine suggesting that the response in the bladder base of horses is mediated predominantly by alpha-1 adrenergic receptors, although alpha-2 receptors also participate.

Adrenergic alpha-Agonists↗

Alpha- and beta-adrenergic receptors in the horse ureter.

The presence of both alpha and beta adrenergic receptors in the caudal third ureter of the horse were studied in vitro under isometric conditions using adrenergic agonist and antagonist drugs. Isoprenaline and the beta 2- stimulating agent, salbutamol, elicited relaxation of the ureter smooth muscle strips. The responses were not affected by the beta 1- blocking agent, practolol, but were totally abolished by propranolol and the beta 2- blocking agent, butoxamine. The stimulation of alpha-adrenergic receptors with noradrenaline and phenylephrine evoked a contractile effect which was totally inhibited by phenoxybenzamine and the alpha 1- blocking agent, prazosin. It is concluded that in the horse ureter the alpha receptors are dominant and belong to alpha 1 subtype while the beta receptors are recessive and belong to beta 2- adrenoceptor subtype.

Animals↗

[Characterization of histaminergic receptors in the urinary bladder of sheep].

The effect of histamine was studied simultaneously on isolated smooth muscle preparations obtained from the body and base of the bladder of sheep. The histamine had a contractile effect mediated specifically through H1 receptors. It appears that the effect of histamine is not mediated through either a cholinergic or an adrenergic mechanism.

Animals↗