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Biomedical subjects

I MacKenzie

Publications and source records attributed to I MacKenzie.

27 records · Page 2Linked to original sources
PubMed1988

Calcium currents in single isolated smooth muscle cells from the rabbit ear artery in normal-calcium and high-barium solutions.

1. Ca2+ inward current was studied using the whole-cell patch clamp technique in single smooth muscle cells enzymatically isolated from the rabbit ear artery. Currents were studied in salt solutions containing either normal (1.5 mM) Ca2+ or high (110 mM) Ba2+. Outward currents were minimized by using a high-Na+ intracellular solution containing 10 mM-TEA. 2. In normal-Ca2+ solution, the threshold at which inward current could be evoked was -60 mV at a holding potential of -80 mV and -48 mV at a holding potential of -60 mV. At both holding potentials, the current showed little inactivation over 500 ms near threshold, and inactivated substantially but incompletely with larger depolarizations. In high-Ba2+ solution where currents were 5-10 times larger, current threshold, maximal peak amplitude and apparent reversal potential were shifted in a positive direction along the voltage axis. 3. Inward current in normal-Ca2+ solution was only fully available negative to -90 mV, was half-inactivated near -47 mV and was about 90% inactivated at -10 mV. A component of non-inactivating current was, however, present in both normal-Ca2+ and high-Ba2+ solutions even after conditioning pulses of 5 s duration to +30 mV. The inactivation-potential relationship was shifted in a positive direction in high-Ba2+ solution, and its position showed considerable variation between cells. 4. The inward current from a holding potential of -70 mV was reduced in normal-Ca2+ solution by about 50% by nifedipine (0.1 microM) in some cells at all test potentials, although at more-negative test potentials peak current was unaffected in some cells even at 10 microM. In some cells when the holding potential was -90 mV, the peak current amplitude was increased markedly by 10 microM-nifedipine. In high-Ba2+ solution, from negative holding potentials (-70 to -80 mV), nifedipine augmented peak current at test potentials negative to -10 mV and shifted the current threshold in a negative direction; current at potentials positive of -10 mV was reduced. Both effects were concentration dependent. The stimulatory effect of nifedipine was abolished and its inhibitory effect was enhanced when less-negative holding potentials were employed. Bay K 8644 (0.1 or 1 microM) approximately doubled current amplitude in normal-Ca2+ solution at a holding potential of -60 or -70 mV, and shifted maximal peak and threshold current in a negative direction. 5. Holding at more-negative potentials made available a component of current which activated and inactivated at more-negative potentials especially in high-Ba2+ solution.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1984

Intestinal absorption of zinc: competitive interactions with iron, cobalt, and copper in mice with sex-linked anemia (sla).

Duodenal uptake and transfer of 59Fe and 65Zn and absorptive interactions between iron, zinc, cobalt, and copper were studied in sla mice and in genetically normal Swiss albino control mice. Genetically normal mice with a high iron-absorbing capacity, induced by being fed an iron-deficient diet, showed greater uptake and transfer of 65Zn in duodenum but not ileum, compared with mice with a low iron-absorbing capacity. 59Fe transfer from the duodenal mucosa to the body was lower in sla mice compared with controls and bleeding stimulated the capacity to absorb 59Fe less in sla mice relative to normal controls. In contrast, 65Zn transfer in sla was no different from controls and was not stimulated by bleeding in sla or in control mice. Iron or cobalt in a 10-fold molar excess predominantly lowered 65Zn transfer in both sla and controls, but in a study of the effect of zinc on iron transport only the uptake of 59Fe in sla mice was lowered by excess zinc in the perfusate. The effect of added copper on 65Zn transport was paradoxical; in both sla and control mice copper markedly increased 65Zn uptake relative to perfusates containing 65Zn alone, but transfer in normal mice was lowered whereas it was increased in sla animals. The interaction between zinc and iron does not appear to take place at the site of the genetic defect in sla mice. The lesion in iron transport in these mice is likely due to defective binding and transfer sites in the basolateral membrane; these sites are apparently exclusive for iron and not shared by zinc.

Anemia↗
PubMed1983

Fetal blood group studies during mid-trimester pregnancy and the management of severe isoimmunization.

Fetal blood samples collected at 14-22 weeks' gestation by fetoscopy have been analysed for 25 different red cell antigens and anti-A antibodies. The results obtained demonstrate that the technique can be used to determine fetal blood groups during mid-pregnancy and also to provide the opportunity to study the physiological and pathological developments of blood groups and their antibodies and to manage more rationally those pregnancies threatened by erythroblastosis fetalis.

Antibodies, Anti-Idiotypic↗
PubMed1983

Studies on the stereoselectivity of the P2-purinoceptor.

ATP, 2-chloro-ATP, 2-methylthio-ATP, and their unnatural L-enantiomers, were synthesized and their effects tested on the guinea-pig taenia coli and urinary bladder, and the stimulated frog ventricle. The potent P2-purinoceptor agonists, 2-chloro-ATP and 2-methylthio-ATP were, respectively, 30 and 200 times more effective than ATP in relaxing the guinea-pig taenia, but approximately as effective as ATP in contracting the guinea-pig bladder and augmenting the force of contraction of the frog ventricle. A high degree of stereoselectivity was observed for relaxations of the guinea-pig taenia coli produced by the P2-purinoceptoragonists, and 2-methylthio-ATP was over 700 times more effective than its L-enantiomer. In contrast, stereoselectivity for contraction of the guinea-pig bladder was observed only at low concentrations with each pair of enantiomers, and a similar low stereoselectivity was displayed by the frog ventricle. These results show that P2-purinoceptors mediating inhibitory responses in the guinea-pig taenia coli can show a high degree of stereoselectivity, while P2-purinoceptors mediating excitatory responses in the guinea-pig bladder and in the frog ventricle show little stereoselectivity. The partial stereoselectivity of the P2-purinoceptor in smooth muscle contrasts with the absolute stereospecificity of P1-purinoceptors for adenosine on smooth muscle and autonomic nerve terminals and the absolute stereospecificity of the receptor for ADP on the human platelet.

Adenosine Triphosphate↗
PubMed1982

The effects of purified botulinum neurotoxin type A on cholinergic, adrenergic and non-adrenergic, atropine-resistant autonomic neuromuscular transmission.

The twitch response observed during low frequency electrical stimulation of postganglionic cholinergic neurones supplying the longitudinal smooth muscle of the guinea-pig ileum was markedly reduced by incubation with an homogeneous preparation of botulinum type A neurotoxin (4.3-8.6 nM). This intoxication of the autonomic cholinergic neurones was long-lasting, irreversible by washing, but readily reversed by 4-aminopyridine (50-1000 microM). The noradrenergic motor response of the rat anococcygeus following field stimulation was partially antagonised by the neurotoxin. The non-adrenergic inhibitory response of the guinea-pig taenia coli, elicited by field stimulation, was not antagonised by botulinum toxin, suggesting that a source of a non-adrenergic inhibitory transmitter exists, other than intramural cholinergic neurones. However, the neurogenic excitatory responses of the guinea-pig bladder, elicited by field stimulation in the presence of atropine and guanethidine, were virtually abolished by botulinum toxin. It is suggested that the parasympathetic neurones which supply the smooth muscle of the guinea-pig urinary bladder co-release acetylcholine and a non-cholinergic excitatory transmitter; ATP or polypeptides are possible candidates.

Adrenergic Fibers↗