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G J Quirk

Publications and source records attributed to G J Quirk.

25 records · Page 2Linked to original sources
PubMed1987

Physiological basis of motor effects of a transient stimulus to cerebral cortex.

This contribution includes a selective review of previously published material, findings from some new experiments, and discussion of some relationships between animal and recent human data. The major questions are: What descends from the cerebral cortex after a brief surface stimulus? What explains the various components of the corticofugal discharge? What are the motor consequences of the corticofugal discharge, and what are the effects of lesions on both? The focus is on the corticospinal system, which through its monosynaptic connection with alpha motoneurons of distal muscles accounts for the short latency movements after a transient cortical stimulus. The pyramidal and lateral corticospinal tract response in monkey or cat to a surface stimulus applied to area 4 is a direct (D) wave conducted in fast axons followed by several indirect (I) waves with a period of greater than 1 ms. Although computer summing reveals, at increasing amplitudes, D and I waves in recordings from nuchal skin, vertebra, and surface of the spinal cord, "killed end" recording is essential to reveal the true extent of I relative to D waves. The D wave might result from excitation of: the initial segment (IS), i.e., the classical spike trigger zone; the first or deeper nodes in white matter; or arborizations of the axon collaterals in gray matter. Under different circumstances, each of these modes of excitation can be effective. Thus, with threshold stimulation through separated bipolar electrodes, intracellular recording from pyramidal tract (PT) and uninvaded motor cortical neurons shows that D activation usually occurs when the membrane potential immediately before the stimulus is relatively depolarized, implying excitation of the IS region, i.e., close to the site of synaptic transfer. A monopolar surface (+) stimulus at the appropriate focus usually generates a D wave at weaker intensity than does a surface (-) stimulus. However, if a little above threshold, stimuli of either polarity generate both D and I waves, but the ratio of D:I amplitude is usually greater with surface (+) stimulation. A theoretical estimate of the depth of excitation by a surface (+) stimulus was consistent with threshold excitation occurring at the first node. Slow PT neurons are excited by surface stimulation, but trivially contribute to population PT or corticospinal recordings. Intracellular recording from PT neurons identifies a monosynaptic excitatory postsynaptic potential as the cause of the first I wave, the period between successive I waves reflecting single delays for synaptic discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Mechanism of action of a new prostaglandin antihypertensive, viprostol [CL 115 347; (dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester]: (II). Effects on the adrenergic nervous system.

Viprostol [(dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester; CL 115 347] is a new orally and transdermally active antihypertensive agent that exerts its major antihypertensive action by vasodilation. The present studies were conducted to examine its effects on the adrenergic nervous system. In cats, viprostol did not inhibit renal sympathetic nerve discharge (RSND) monitored at the postganglionic region, indicating that nerve transmission or conduction was not blocked at the ganglion or the pre- or postganglionic fibres. In cat nictitating membrane preparations in situ, viprostol partially blocked the membrane contractile response to exogenous epinephrine and norepinephrine, as well as to electrical stimulation of pre- and postganglionic fibres. In spontaneously hypertensive rats (SHR), viprostol partially blocked the vasopressor response of exogenous norepinephrine and epinephrine specifically without influencing that of angiotensin II. All these suggest that viprostol produced weak alpha-adrenoceptor blockade. Viprostol did not antagonize the tachycardia induced by stimulation of the discrete segments at C7-T1 (cardio-accelerator) of the spinal cord in pithed SHR, suggesting that viprostol did not activate the presynaptic alpha-adrenoceptors. Viprostol significantly inhibited the increase in blood pressure induced by electrical stimulation of the spinal cord at T7-T9 in pithed SHR, probably due to postsynaptic alpha-adrenoceptor blockade. In conclusion, viprostol produced weak, but statistically significant alpha-adrenoceptor blockade which may contribute partially to its antihypertensive action.

Angiotensin I↗
PubMed1984

The diuretic effects of CL 115,129 (d,1-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2) and l-prostaglandin E2 in dogs.

CL 115,129, the corresponding carboxylic acid and major metabolite of CL 115,347 (d,1-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester), a potent orally and transdermally long acting antihypertensive agent, infused at 0.1 microgram/kg/min into the left renal artery of sodium pentobarbital anesthetized beagle dogs increased urinary volume, sodium (Na+), potassium (K+) and chloride (Cl-) excretion of the left kidney 289, 201, 101 and 229%, respectively, over the 30 min vehicle-treated control periods. At 0.3 microgram/kg/min CL 115,129 caused a 475 and 336% increase in urinary volume and Na+, respectively. l-Prostaglandin E2 (l-PGE2) infused at 0.1 microgram/kg/min into the left renal artery increased urinary volume, Na+, K+ and Cl- excretion of the left kidney of anesthetized beagle dogs 416, 234, 112 and 255%, respectively, over the control. Both CL 115,129 and l-PGE2 did not affect the systemic arterial blood pressure or the electrolyte excretion of the contralateral kidney. It is concluded that in contrast to other conventional vasodilators, which may cause severe water and electrolyte retention, CL 115,347, via its metabolite CL 115,129, may cause diuresis and natriuresis in many clinical settings when used as an antihypertensive.

Animals↗
PubMed1984

Evidence for the lack of interaction between (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine and alpha-adrenoceptors in vivo and in vitro.

The interactions of (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine (octadecyl-AGPC) with alpha-adrenoceptors were studied in rat mesenteric artery, cat nictitating membrane and on the blood pressure of the cat and spontaneously hypertensive (SH) rat. Using a direct radioligand alpha-adrenoceptor binding assay in particulate fractions of rat mesenteric arteries, octadecyl-AGPC was found to be 5 X 10(7) and 75 times less potent than prazosin and noradrenaline (NA), respectively, in displacing (2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane ([3H]-WB 4101--a selective probe for the identification of alpha-adrenoceptors). In the cat, intravenous infusions of octadecyl-AGPC, which produce a hypotensive response, did not attenuate nictitating membrane contractions in vivo in response to intravenous injections of NA, adrenaline (Ad) or to electrical stimulation of the postganglionic fibres of the superior cervical ganglion. In these experiments, the pressor responses to NA or Ad were not affected by octadecyl-AGPC. Phentolamine, on the other hand, attenuated nictitating membrane contractions and blood pressure responses to Ad or NA. In the SH rat, octadecyl-AGPC decreased mean arterial blood pressure (MABP). After an intravenous dose of phentolamine which lowered MABP, the depressor response to octadecyl-AGPC was reduced. When MABP in the phentolamine-treated SH rat was restored to its initial level with an infusion of angiotensin II (AII), the depressor response to octadecyl-AGPC was restored to its original magnitude. The effectiveness of alpha-adrenoceptor blockade under these experimental conditions was monitored with intravenous NA and Ad. Thus, based on radioligand binding studies and pharmacological studies, it is concluded that octadecyl-AGPC lacks the ability to interact with alpha-adrenoceptors.

Angiotensin II↗
PubMed1983

Antihypertensive activity of dl-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl prostaglandin E2 methyl ester (CL 115,347), a new orally and transdermally long-acting antihypertensive agent.

CL 115,347 [dl-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl prostaglandin E2 methyl ester] has a broad spectrum of antihypertensive activity in many animal hypertension models in every species tested. In conscious spontaneously hypertensive rats, CL 115,347 at 0.25 to 10 mg/kg orally produced 31 to 53 mm Hg lowering of the mean arterial blood pressure (MABP) with a duration of action of 1 to greater than 8 hr. When applied transdermally, CL 115,347 was more potent and longer acting than by the oral route. At 0.03 to 1 mg/kg, topically applied CL 115,347 lowered MABP of spontaneously hypertensive rats 27 to 46 mm Hg. Duration of action was greater than 6 to greater than 24 hr. CL 115,347 was also active in conscious normotensive rats (-27 mm Hg), deoxycorticosterone-salt-induced hypertensive rats (-51 mm Hg) and aorta-coarcted hypertensive rats (-52 mm Hg) when tested at 1 mg/kg orally. At 3 mg/kg orally, CL 115,347 lowered MABP of Dahl "S" salt-sensitive rats 55 mm Hg. CL 115,347 orally and s.c. lowered MABP in two-kidney, one-clip Goldblatt renal hypertensive dogs and was accompanied by tachycardia. CL 115,347, at 0.1 and 0.2 mg/kg orally, maximally lowered the systolic blood pressure of conscious rhesus monkeys 33 to 63 mm Hg with only a slight increase in heart rate. Therefore, CL 115,347 was antihypertensive in animals with low, normal and high plasma renin activity. The present findings suggest that CL 115,347 may be useful for the treatment of human hypertension.

Administration, Oral↗
PubMedDate not supplied

A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex.

The effects of different orientations of a Cadwell round magnetic coil (MC) were compared with each other and with surface electrical stimulation of motor cortex in monkeys anesthetized with pentobarbital or urethane. Recordings were made from within the lateral corticospinal tract, either from axonal populations or with a microelectrode from individual axons. A lateral-sagittally orientated MC directly excited corticospinal neurons at lower stimulus intensity than was required for indirect, i.e., transsynaptic excitation via inputs to corticospinal neurons. By contrast, in 2 out of 3 macaques tested, a vertex-tangential orientation could excite corticospinal neurons indirectly at lower intensities than were required for direct excitation; at higher intensities, direct excitation also occurred. The site of direct corticospinal excitation by a lateral-sagittally orientated MC was inferred by comparing the response variability and latency to MC and surface electrical stimuli. Cathodal stimuli elicited more variable corticospinal population responses and later individual axonal responses than were obtained with anodal stimuli. The variability in response is attributed to interaction between nearby, on-going synaptic bombardment and the stimulus, implying that surface cathodal stimuli directly activate corticospinal neurons at the spike trigger zone (presumably the initial segment). By contrast, the consistency and reduced latency of the corticospinal responses to surface anodal stimuli are attributed to the direct excitation of corticospinal fibers within the white matter. When the stimulus intensity is clearly above threshold, surface anodal and cathodal stimuli can activate corticospinal neurons both directly and indirectly. Direct corticospinal excitation by the MC can resemble the effects of either surface anodal or surface cathodal stimuli. We conclude that the MC can activate corticospinal neurons at the spike trigger zone or their fibers deeper in white matter. The findings in the monkey are used to interpret the effects of different MC orientations in the human.

Action Potentials↗